| S1130 | 
                                    
                                        
                                        
                                            Sepantronium Bromide (YM155)
                                        
                                     | 
                                    Sepantronium Bromide(YM155) is a potent survivin suppressant by inhibiting Survivin promoter activity with IC50 of 0.54 nM in HeLa-SURP-luc and CHO-SV40-luc cells; does not significantly inhibit SV40 promoter activity, but is observed to slightly inhibit the interaction of Survivin with XIAP. YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells. Phase 2. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Cell Rep Med, 2025, S2666-3791(25)00102-8
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Biochim Biophys Acta Mol Basis Dis, 2025, 1871(3):167693
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cancer Res Commun, 2025, 5(6):1018-1033
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                            
                                                 
                                            
                                        
                                     | 
                                
                            
                                
                                    | S7015 | 
                                    
                                        
                                        
                                            Birinapant
                                        
                                     | 
                                    Birinapant is a SMAC mimetic antagonist, mostly to cIAP1 with Kd of <1 nM in a cell-free assay, less potent to XIAP. Birinapant helps to induce apoptosis in latent HIV-1-infected cells. Phase 2. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        EMBO Mol Med, 2025, 10.1038/s44321-025-00201-x
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Infect Immun, 2025, 93(3):e0032424
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Nat Biomed Eng, 2024, 10.1038/s41551-024-01273-9
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                            
                                                 
                                            
                                        
                                     | 
                                
                            
                                
                                    | S7597 | 
                                    
                                        
                                        
                                            BV-6
                                        
                                     | 
                                    BV-6 is a SMAC mimetic, dual cIAP and XIAP inhibitor. 
 | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Nat Commun, 2025, 16(1):4919
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        EMBO J, 2025, 10.1038/s44318-025-00561-7
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cell Death Dis, 2025, 16(1):476
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                            
                                                 
                                            
                                        
                                     | 
                                
                            
                                
                                    | S7009 | 
                                    
                                        
                                        
                                            LCL161
                                        
                                     | 
                                    LCL-161, a small molecule second mitochondrial activator of caspase (SMAC) mimetic, potently binds to and inhibits multiple IAPs (i.e. XIAP, c-IAP). | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Immunity, 2025, 58(4):961-979.e8
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Nat Commun, 2025, 16(1):4919
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        EMBO Mol Med, 2025, 10.1038/s44321-025-00201-x
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                            
                                                 
                                            
                                        
                                     | 
                                
                            
                                
                                    | S2754 | 
                                    
                                        
                                        
                                            Xevinapant (AT406)
                                        
                                     | 
                                    Xevinapant (AT406, ARRY-334543, Debio1143, SM-406) is a potent Smac mimetic and an antagonist of IAP (inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide. Phase 1. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Nat Commun, 2025, 16(1):2572
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cell Death Dis, 2025, 16(1):476
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        bioRxiv, 2025, 2025.09.22.677496
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                            
                                                 
                                            
                                        
                                     | 
                                
                            
                                
                                    | S7010 | 
                                    
                                        
                                        
                                            GDC-0152
                                        
                                     | 
                                    GDC-0152 is a potent antagonist of XIAP-BIR3, ML-IAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 28 nM, 14 nM, 17 nM and 43 nM in cell-free assays, respectively; less affinity shown to cIAP1-BIR2 and cIAP2-BIR2. Phase 1. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        J Exp Clin Cancer Res, 2024, 43(1):311
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Nat Commun, 2023, 14(1):1461
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cell Rep, 2023, 42(1):111965
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                            
                                                 
                                            
                                        
                                     | 
                                
                            
                                
                                    | S7362 | 
                                    
                                        
                                        
                                            AZD5582
                                        
                                     | 
                                    AZD5582, a novel small-molecule IAP inhibitor, binds potently to the BIR3 domains of cIAP1, cIAP2, and XIAP with IC50 values of 15, 21, and 15  | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        EMBO J, 2025, 10.1038/s44318-025-00412-5
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cell Rep, 2024, 43(7):114400
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cell Death Dis, 2023, 14(9):599
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                     | 
                                
                            
                                
                                    | S7089 | 
                                    
                                        
                                        
                                            SM-164
                                        
                                     | 
                                    SM-164 is a potent, non-peptide, cell-permeable antagonist of XIAP that targets both the BIR2 and BIR3 domains with IC50 of 1.39 nM. SM-164 induces apoptosis and tumor regression. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        EMBO J, 2025, 10.1038/s44318-025-00412-5
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        J Virol, 2025, 99(3):e0198024
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Autoimmunity, 2025, 58(1):2515825
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                     | 
                                
                            
                                
                                    | S7025 | 
                                    
                                        
                                        
                                            Embelin
                                        
                                     | 
                                    Embelin (Embelic Acid, NSC 91874), a quinone isolated from the Japanese Ardisia herb, is an inhibitor of X-linked inhibitor of apoptosis (XIAP) with IC50 of 4.1 μM in a cell-free assay. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Heliyon, 2023, 9(3):e14006
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cancers (Basel), 2021, 13(14)3585
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cell Host Microbe, 2018, 24(5):689-702
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
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                                     | 
                                
                            
                                
                                    | S8681 | 
                                    
                                        
                                        
                                            Tolinapant (ASTX660)
                                        
                                     | 
                                    Tolinapant (ASTX660) is a potent, non-peptidomimetic antagonist of cIAP1/2 and XIAP that inhibits the interactions between a SMAC-derived peptide and the BIR3 domains of XIAP (BIR3-XIAP) and cIAP1 (BIR3-cIAP1) with IC50 values less than 40 and 12 nmol/L, respectively. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Cell Death Differ, 2024, 31(10):1318-1332
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Cell Death Differ, 2024, 10.1038/s41418-024-01316-3
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        bioRxiv, 2024, 2024.12.12.628190
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                     | 
                                    
                                        
                                     | 
                                
                            
                                
                                    | S5967 | 
                                    
                                        
                                        
                                            Berberine chloride hydrate
                                        
                                     | 
                                    Berberine (Natural Yellow 18) chloride hydrate is a quaternary ammonium salt from the group of isoquinoline alkaloids. Berberine activates caspase 3 and caspase 8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c. Berberine chloride decreases the expression of c-IAP1, Bcl-2 and Bcl-XL. Berberine chloride induces apoptosis with sustained phosphorylation of JNK and p38 MAPK, as well as generation of the ROS. Berberine chloride is a dual topoisomerase I and II inhibitor. Berberine chloride is also a potential autophagy modulator. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Front Biosci (Landmark Ed), 2022, 27(8):242
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Front Pharmacol, 2021, 12:632201
                                                    
 
                                                 
                                            
                                        
                                     | 
                                    
                                        
                                     | 
                                
                            
                                
                                    | S9634 | 
                                    
                                        
                                        
                                            Phenoxodiol (Haginin E)
                                        
                                     | 
                                    Phenoxodiol (Haginin E, Idronoxil, Dehydroequol, NV 06, PXD) is an isoflavone analog with antineoplastic activity that activates the caspase system, inhibits XIAP (X-linked inhibitor of apoptosis), and disrupts FLICE inhibitory protein (FLIP) expression, resulting in tumor cell apoptosis. Phenoxodiol also inhibits DNA topoisomerase II. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Anticancer Res, 2018, 38(10):5709-5716
                                                    
 
                                                 
                                            
                                        
                                     | 
                                    
                                        
                                     | 
                                
                            
                                
                                    | F0515 | 
                                    
                                        
                                            
                                                XIAP Antibody [J5B21]
                                            
                                        
                                        
                                     | 
                                     | 
                                    
                                        
                                     | 
                                    
                                        
                                     | 
                                
                            
                                
                                    | F0516 | 
                                    
                                        
                                            
                                                c-IAP1 Antibody [F9A20]
                                            
                                        
                                        
                                     | 
                                     | 
                                    
                                        
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                                     | 
                                
                            
                                
                                    | S2271 | 
                                    
                                        
                                        
                                            Berberine chloride
                                        
                                     | 
                                    Berberine chloride is a quaternary ammonium salt from the group of isoquinoline alkaloids. Berberine activates caspase 3 and caspase 8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c. Berberine chloride decreases the expression of c-IAP1, Bcl-2 and Bcl-XL. Berberine chloride induces apoptosis with sustained phosphorylation of JNK and p38 MAPK, as well as generation of the ROS. Berberine chloride is a dual topoisomerase I and II inhibitor. Berberine chloride is also a potential autophagy modulator. | 
                                    
                                        
                                            
                                                
                                                    - 
                                                        Adv Healthc Mater, 2023, e2300591.
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Transl Oncol, 2023, 35:101712
                                                    
 
                                                 
                                            
                                        
                                            
                                                
                                                    - 
                                                        Nat Prod Commun, 2023, 18(3): 1–7
                                                    
 
                                                 
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
                                            
                                        
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                                     | 
                                
                            
                                
                                    | S5600 | 
                                    
                                        
                                        
                                            Flavokawain A
                                        
                                     | 
                                    Flavokawain A, extracted from kava, is an apoptotic inducers and anticarcinogenic agent. Flavokawain A can down-regulation of antiapoptotic proteins, such as XIAP, survivin, and Bcl-xL, thereby changing the balance between apoptotic and antiapoptotic molecules and then induce cell death in tumor cells. | 
                                    
                                        
                                     | 
                                    
                                        
                                     | 
                                
                            
                        
                    
                    
                        
                        
                            
                                
                                    
                                        | S1130 | 
                                        
                                            
                                            Sepantronium Bromide (YM155)
                                                    
                                         | 
                                        Sepantronium Bromide(YM155) is a potent survivin suppressant by inhibiting Survivin promoter activity with IC50 of 0.54 nM in HeLa-SURP-luc and CHO-SV40-luc cells; does not significantly inhibit SV40 promoter activity, but is observed to slightly inhibit the interaction of Survivin with XIAP. YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells. Phase 2. | 
                                        
                                            
                                                
                                                    
                                                        - Cell Rep Med, 2025, S2666-3791(25)00102-8
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Biochim Biophys Acta Mol Basis Dis, 2025, 1871(3):167693
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cancer Res Commun, 2025, 5(6):1018-1033
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
 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                                         | 
                                    
                                
                                    
                                        | S7597 | 
                                        
                                            
                                            BV-6
                                                    
                                         | 
                                        BV-6 is a SMAC mimetic, dual cIAP and XIAP inhibitor. 
 | 
                                        
                                            
                                                
                                                    
                                                        - Nat Commun, 2025, 16(1):4919
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - EMBO J, 2025, 10.1038/s44318-025-00561-7
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cell Death Dis, 2025, 16(1):476
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
         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                                         | 
                                    
                                
                                    
                                        | S7009 | 
                                        
                                            
                                            LCL161
                                                    
                                         | 
                                        LCL-161, a small molecule second mitochondrial activator of caspase (SMAC) mimetic, potently binds to and inhibits multiple IAPs (i.e. XIAP, c-IAP). | 
                                        
                                            
                                                
                                                    
                                                        - Immunity, 2025, 58(4):961-979.e8
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Nat Commun, 2025, 16(1):4919
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - EMBO Mol Med, 2025, 10.1038/s44321-025-00201-x
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                         | 
                                        
                                            
                                                
                                                     
                                                
                                            
                                         | 
                                    
                                
                                    
                                        | S7362 | 
                                        
                                            
                                            AZD5582
                                                    
                                         | 
                                        AZD5582, a novel small-molecule IAP inhibitor, binds potently to the BIR3 domains of cIAP1, cIAP2, and XIAP with IC50 values of 15, 21, and 15  | 
                                        
                                            
                                                
                                                    
                                                        - EMBO J, 2025, 10.1038/s44318-025-00412-5
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cell Rep, 2024, 43(7):114400
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cell Death Dis, 2023, 14(9):599
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
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                                         | 
                                    
                                
                                    
                                        | S7025 | 
                                        
                                            
                                            Embelin
                                                    
                                         | 
                                        Embelin (Embelic Acid, NSC 91874), a quinone isolated from the Japanese Ardisia herb, is an inhibitor of X-linked inhibitor of apoptosis (XIAP) with IC50 of 4.1 μM in a cell-free assay. | 
                                        
                                            
                                                
                                                    
                                                        - Heliyon, 2023, 9(3):e14006
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cancers (Basel), 2021, 13(14)3585
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cell Host Microbe, 2018, 24(5):689-702
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
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                                         | 
                                    
                                
                                    
                                        | S5967 | 
                                        
                                            
                                            Berberine chloride hydrate
                                                    
                                         | 
                                        Berberine (Natural Yellow 18) chloride hydrate is a quaternary ammonium salt from the group of isoquinoline alkaloids. Berberine activates caspase 3 and caspase 8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c. Berberine chloride decreases the expression of c-IAP1, Bcl-2 and Bcl-XL. Berberine chloride induces apoptosis with sustained phosphorylation of JNK and p38 MAPK, as well as generation of the ROS. Berberine chloride is a dual topoisomerase I and II inhibitor. Berberine chloride is also a potential autophagy modulator. | 
                                        
                                            
                                                
                                                    
                                                        - Front Biosci (Landmark Ed), 2022, 27(8):242
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Front Pharmacol, 2021, 12:632201
 
                                                     
                                                
                                            
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                                         | 
                                    
                                
                                    
                                        | S9634 | 
                                        
                                            
                                            Phenoxodiol (Haginin E)
                                                    
                                         | 
                                        Phenoxodiol (Haginin E, Idronoxil, Dehydroequol, NV 06, PXD) is an isoflavone analog with antineoplastic activity that activates the caspase system, inhibits XIAP (X-linked inhibitor of apoptosis), and disrupts FLICE inhibitory protein (FLIP) expression, resulting in tumor cell apoptosis. Phenoxodiol also inhibits DNA topoisomerase II. | 
                                        
                                            
                                                
                                                    
                                                        - Anticancer Res, 2018, 38(10):5709-5716
 
                                                     
                                                
                                            
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                                         | 
                                    
                                
                                    
                                        | S2271 | 
                                        
                                            
                                            Berberine chloride
                                                    
                                         | 
                                        Berberine chloride is a quaternary ammonium salt from the group of isoquinoline alkaloids. Berberine activates caspase 3 and caspase 8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c. Berberine chloride decreases the expression of c-IAP1, Bcl-2 and Bcl-XL. Berberine chloride induces apoptosis with sustained phosphorylation of JNK and p38 MAPK, as well as generation of the ROS. Berberine chloride is a dual topoisomerase I and II inhibitor. Berberine chloride is also a potential autophagy modulator. | 
                                        
                                            
                                                
                                                    
                                                        - Adv Healthc Mater, 2023, e2300591.
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Transl Oncol, 2023, 35:101712
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Nat Prod Commun, 2023, 18(3): 1–7
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
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                                         | 
                                    
                                
                                    
                                        | S5600 | 
                                        
                                            
                                            Flavokawain A
                                                    
                                         | 
                                        Flavokawain A, extracted from kava, is an apoptotic inducers and anticarcinogenic agent. Flavokawain A can down-regulation of antiapoptotic proteins, such as XIAP, survivin, and Bcl-xL, thereby changing the balance between apoptotic and antiapoptotic molecules and then induce cell death in tumor cells. | 
                                        
                                            
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                                        | S7015 | 
                                        
                                            Birinapant
                                         | 
                                        Birinapant is a SMAC mimetic antagonist, mostly to cIAP1 with Kd of <1 nM in a cell-free assay, less potent to XIAP. Birinapant helps to induce apoptosis in latent HIV-1-infected cells. Phase 2. | 
                                        
                                            
                                                
                                                    
                                                        - EMBO Mol Med, 2025, 10.1038/s44321-025-00201-x
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Infect Immun, 2025, 93(3):e0032424
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Nat Biomed Eng, 2024, 10.1038/s41551-024-01273-9
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                     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                                         | 
                                    
                                
                                    
                                        | S2754 | 
                                        
                                            Xevinapant (AT406)
                                         | 
                                        Xevinapant (AT406, ARRY-334543, Debio1143, SM-406) is a potent Smac mimetic and an antagonist of IAP (inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide. Phase 1. | 
                                        
                                            
                                                
                                                    
                                                        - Nat Commun, 2025, 16(1):2572
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cell Death Dis, 2025, 16(1):476
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - bioRxiv, 2025, 2025.09.22.677496
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                         | 
                                        
                                            
                                                
                                                     
                                                
                                            
                                         | 
                                    
                                
                                    
                                        | S7010 | 
                                        
                                            GDC-0152
                                         | 
                                        GDC-0152 is a potent antagonist of XIAP-BIR3, ML-IAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 28 nM, 14 nM, 17 nM and 43 nM in cell-free assays, respectively; less affinity shown to cIAP1-BIR2 and cIAP2-BIR2. Phase 1. | 
                                        
                                            
                                                
                                                    
                                                        - J Exp Clin Cancer Res, 2024, 43(1):311
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Nat Commun, 2023, 14(1):1461
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cell Rep, 2023, 42(1):111965
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
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                                         | 
                                    
                                
                                    
                                        | S7089 | 
                                        
                                            SM-164
                                         | 
                                        SM-164 is a potent, non-peptide, cell-permeable antagonist of XIAP that targets both the BIR2 and BIR3 domains with IC50 of 1.39 nM. SM-164 induces apoptosis and tumor regression. | 
                                        
                                            
                                                
                                                    
                                                        - EMBO J, 2025, 10.1038/s44318-025-00412-5
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - J Virol, 2025, 99(3):e0198024
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Autoimmunity, 2025, 58(1):2515825
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
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                                         | 
                                    
                                
                                    
                                        | S8681 | 
                                        
                                            Tolinapant (ASTX660)
                                         | 
                                        Tolinapant (ASTX660) is a potent, non-peptidomimetic antagonist of cIAP1/2 and XIAP that inhibits the interactions between a SMAC-derived peptide and the BIR3 domains of XIAP (BIR3-XIAP) and cIAP1 (BIR3-cIAP1) with IC50 values less than 40 and 12 nmol/L, respectively. | 
                                        
                                            
                                                
                                                    
                                                        - Cell Death Differ, 2024, 31(10):1318-1332
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - Cell Death Differ, 2024, 10.1038/s41418-024-01316-3
 
                                                     
                                                
                                            
                                                
                                                    
                                                        - bioRxiv, 2024, 2024.12.12.628190
 
                                                     
                                                
                                            
                                                
                                            
                                                
                                            
                                                
                                            
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