TGF-beta/Smad Inhibitors

Cat.No.	Product Name	Information	Product Use Citations
S1476	SB-525334	SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM in a cell-free assay, 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6.	J Control Release, 2025, S0168-3659(25)00029-X Commun Biol, 2025, 8(1):152 Sci Rep, 2025, 15(1):25926
S7146	DMH1	DMH1 is a selective BMP receptor inhibitor with IC50 of 107.9 nM for ALK2, exhibiting no inhibition on AMPK, ALK5, KDR (VEGFR-2) or PDGFR. This compound inhibits autophagy.	Cell Stem Cell, 2025, S1934-5909(25)00081-5 Nat Commun, 2025, 16(1):10435 J Adv Res, 2025, S2090-1232(25)00553-3
S2907	Pirfenidone	Pirfenidone is an inhibitor for TGF-β production and TGF-β stimulated collagen production, reduces production of TNF-α and IL-1β, and also has anti-fibrotic and anti-inflammatory properties. Pirfenidone attenuates chemokine (CC motif) ligand-2 (CCL2) and CCL12 production with anti-fibrotic activity. Phase 3.	Biomed Pharmacother, 2025, 188:118216 Eur Respir J, 2024, 2300580 Phytomedicine, 2024, 135:156051
S2805	LY364947	LY364947 (HTS 466284) is a potent ATP-competitive inhibitor of TGFβR-I with IC50 of 59 nM in a cell-free assay, shows 7-fold selectivity over TGFβR-II.	Adv Sci (Weinh), 2024, 11(4):e2304987 Cell Rep Med, 2024, 5(2):101416 Cell Commun Signal, 2024, 22(1):242
S2186	SB505124	SB505124 is a selective inhibitor of TGFβR for ALK4, ALK5 with IC50 of 129 nM and 47 nM in cell-free assays, respectively, also inhibits ALK7, but does not inhibit ALK1, 2, 3, or 6.	Nat Commun, 2025, 16(1):10435 Cell Rep, 2025, 44(5):115675 Calcif Tissue Int, 2025, 116(1):57
S2750	GW788388	GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM in a cell-free assay, also inhibits TGF-β type II receptor and activin type II receptor activities, but does not inhibit BMP type II receptor.	Mol Carcinog, 2024, 10.1002/mc.23715 J Biol Chem, 2023, 299(4):103017 proquest, 2023,
S7359	K02288	K02288 is a potent, and selective type I BMP receptor inhibitor with IC50 of 1.1, 1.8, 6.4 nM for ALK2, ALK1 and ALK6, showing weaker inhibition on other ALKs (3, 4, 5) and ActRIIA.	FEBS J, 2024, 291(2):272-291 J Neurooncol, 2024, 10.1007/s11060-024-04625-2 Nat Commun, 2022, 13(1):2844
S7624	SD-208	SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, >100-fold selectivity over TGF-βRII.	J Cancer, 2024, 15(9):2448-2459 JCI Insight, 2023, 8(3)e166688 Cancers (Basel), 2023, 10.3390/cancers15205086
S3552	SIS3	SIS3 is a cell-permeable inhibitor of Smad3 that selectively inhibits TGF-β1-dependent Smad3 phosphorylation and Smad3-mediated cellular signaling. This compound reduces TGF-β1-induced type 1 procollagen expression and myofibroblast differentiation in normal dermal fibroblasts as well as scleroderma fibroblasts.	J Virol, 2025, 99(9):e0043525 Life Sci Alliance, 2024, 7(6)e202302408 Front Bioeng Biotechnol, 2023, 11:1281157
S6713	ITD-1	ITD-1 is a potent TGF-β inhibitor. It does not block the kinase activity of either type I (TGFBR1) or type II (TGFBR2) TGFβ receptors but potently blocks phosphorylation of the effector SMAD2/3 proteins induced by TGFβ2, and only minimally in response to Activin A.	World J Gastrointest Oncol, 2025, 17(1):97831 Redox Biol, 2024, 76:103349 Cell Oncol (Dordr), 2024, 10.1007/s13402-024-00989-9
S7658	Kartogenin	Kartogenin (KGN) is an activator of the smad4/smad5 pathway, and promotes the selective differentiation of multipotent mesenchymal stem cells into chondrocytes.	Sci Rep, 2024, 14(1):15022 Pharmaceutics, 2023, 15(7)1949 Int J Mol Sci, 2022, 24(1)390
S7147	LDN-212854	LDN-212854 (BMP Inhibitor III) is a potent and selective BMP receptor inhibitor with IC50 of 1.3 nM for ALK2, about 2-, 66-, 1641-, and 7135-fold selectivity over ALK1, ALK3, ALK4, and ALK5, respectively.	EMBO Rep, 2024, 25(7):3090-3115 Am J Pathol, 2023, S0002-9440(23)00047-0 Am J Pathol, 2023, 193(5):532-547
S8700	TP0427736 HCl	TP0427736 is a potent inhibitor of ALK5 kinase activity with an IC50 of 2.72 nM and this effect is 300-fold higher than the inhibitory effect on ALK3 (IC50 = 836 nM for ALK3). It also inhibits Smad2/3 phosphorylation in A549 cells induced by TGF-β1 with an IC50 value of 8.68 nM.	Commun Biol, 2023, 6(1):824 Nutrients, 2023, 16(1)64 Int J Mol Sci, 2023, 24(19)14444
S7148	ML347	ML347 (LDN-193719) is a selective BMP receptor inhibitor with IC50 of 32 nM for ALK2, >300-fold selectivity over ALK3. This compound also inhibits ALK1 activity with IC50 of 46 nM.	Development, 2022, 149(20)dev192310 Biomolecules, 2020, 10(4)E519 Biomolecules, 2020, 29;10(4) pii: E519
S8772	LY 3200882	LY 3200882 is a potent, highly selective inhibitor of TGF-β receptor type 1 (TGFβRI). It potently inhibits TGFβ mediated SMAD phosphorylation in vitro in tumor and immune cells and in vivo in subcutaneous tumors in a dose dependent fashion.	J Inflamm Res, 2021, 14:2897-2911 Pediatr Rheumatol Online J, 2021, 19(1):72 Br J Cancer, 2020, 10.1038/s41416-020-01040-y
S7627	LDN-214117	LDN-214117 is a potent and selective BMP type I receptor kinase ALK2 inhibitor with IC50 of 24 nM.	Cancer Res, 2024, 10.1158/0008-5472.CAN-23-2631 bioRxiv, 2023, 2023.06.14.544941 FASEB J, 2021, 35(3):e21263
S2308	Hesperetin	Hesperetin is a bioflavonoid and, to be more specific, a flavanone.	J Transl Med, 2024, 22(1):208 Sci Rep, 2022, 12(1):7 Front Pharmacol, 2021, 12:735087
S8318	Alantolactone	Alantolactone, a naturally occurring eudesmane-type sesquiterpene lactone (SL), could induce activin/SMAD3 signaling and disrupt Cripto-1/activin receptor type II A interaction.	Molecules, 2024, 29(8)1866 Nat Commun, 2022, 13(1):107 Onco Targets Ther, 2017, 10:1767-1776
E2394	TGFβRI-IN-3	TGFβRI-IN-3 represents a highly selective TGFβR1 inhibitor that has potential applications in immuno-oncology, inhibits TGFβR1 at an IC50 of 0.79 nM with 2000-fold selectivity against MAP4K4.	Nutrients, 2024, 16(17)2991 JCI Insight, 2023, e161563
S7710	R-268712	R-268712 is a potent and selective inhibitor of ALK5 with an IC50 of 2.5 nM.	Kidney360, 2025, 10.34067/KID.0000000852
S3223	L-Quebrachitol	L-Quebrachitol (L-QCT), a natural product isolated from many plants, promotes proliferation and cell DNA synthesis. This compound upregulates bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2) and regulatory genes associated with mitogen-activated protein kinase (MAPK) and Wnt/β-catenin signaling pathway, while down-regulating the receptor activator of the nuclear factor-κB(NF-κB) ligand (RANKL) mRNA level.
E4798	SRI-011381 hydrochloride	SRI-011381 hydrochloride is an agonist of the transforming growth factor-beta (TGF-β) signalling pathway and exhibits neuroprotective effects with the potential to treat Alzheimer's disease. It also increases fibronectin expression in the NIH‐3T3 cells stimulated by metformin.
S0523	SB 4	SB 4 is a potent and selective agonist of bone morphogenetic protein 4 (BMP4) signaling with EC50 of 74 nM. This compound enhances canonical BMP signaling and activates SMAD-1/5/9 phosphorylation. As an agonist of the BMP signaling pathway, this chemical can significantly upregulate the expression levels of classical BMP4 downstream target genes (such as DNA binding inhibitors Id1 and Id3).
E3859	Lycopus Extract	Lycopus Extract is extracted from Lycopus, which ameliorate podocytes injury by inhibiting TGF-β signaling pathway.
S2234	BIBF-0775	BIBF-0775 is a selective inhibitor of transforming growth factor β Receptor I (TGFβRI,Alk5) with an IC50 of 34nM.
S0153	SJ000291942	SJ000291942 is a canonical bone morphogenetic proteins (BMP) signaling pathway activator.
E6646^New	BMS-986260	BMS-986260 is an orally active immuno-oncology agent that inhibits TGFβR1 with an IC50 of 1.6 nM. It shows selectivity for TGFβR1 compared to TGFβR2 and over 200 other kinases. In MINK and NHLF cell lines, BMS-986260 blocks TGFβ-induced pSMAD2/3 nuclear translocation with IC50 values of 350 nM and 190 nM, respectively.
E1785	PF-06952229	PF-06952229(UNII-1KKS7U3X86) is a selective, orally available inhibitor of the serine/threonine kinase TGF-β receptor 1 (TGF-β-R1). It inhibits pSMAD2 in both tumor and immune cells, reducing TGF-β signalling and reversing EMT in vitro. It modulates the tumor immune microenvironment and shows antitumor activity in mouse models.
S7306	Dorsomorphin Dihydrochloride	Dorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line.	J Clin Invest, 2025, e190215 Redox Biol, 2025, 81:103532 Redox Biol, 2025, 82:103606
S7840	Dorsomorphin (Compound C)	Dorsomorphin is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy. For cell testing, the water-soluble S7306 Dorsomorphin (Compound C) 2HCl is recommended.	Nucleic Acids Res, 2025, 53(22)gkaf1397 Theranostics, 2025, 15(12):5931-5952 EMBO Mol Med, 2025, 17(10):2735-2761
S1576	Sulfasalazine	Sulfasalazine is a sulfa derivative of mesalazine, used as an anti-inflammatory agent to treat bowel disease and rheumatoid arthritis. This compound is a potent and specific inhibitor of nuclear factor kappa B (NF-κB), TGF-β and COX-2. It induces ferroptosis, apoptosis and autophagy.	Med Oncol, 2024, 41(8):188 Adv Sci (Weinh), 2023, 10(20):e2300517 Proc Natl Acad Sci U S A, 2022, 119(36):e2117396119
S8144	Halofuginone	Halofuginone (RU-19110) is the competitively inhibitor of prolyl-tRNA synthetase with Ki of 18.3 nM.It could also down-regulate Smad3 and blocked TGF-β signaling at 10 ng/ml in mammal.	Sci Adv, 2025, 11(28):eadw1883 Cell Rep, 2024, 43(9):114728 J Neurochem, 2024, 10.1111/jnc.16102
S7914	ISX-9 (Isoxazole 9)	Isoxazole 9 (Isx-9) is a synthetic promotor of adult neurogenesis by triggering neuronal differentiation of adult neural stem/precursor cells (NSPCs). Isoxazole 9 (Isx-9) activates multiple pathways including TGF-β induced epithelial–mesenchymal transition (EMT) signaling, canonical and non-canonical Wnt signaling at different stages of cardiac differentiation.	iScience, 2025, 28(3):112015 Front Cell Dev Biol, 2025, 13:1513163 Cell Regen, 2025, 14(1):18
S5183	PD 169316	PD 169316 is a potent, selective and cell-permeable p38 MAP kinase inhibitor with IC50 of 89 nM. PD169316 abrogates signaling initiated by both TGFbeta and Activin A. PD169316 shows antiviral activity against Enterovirus71.	J Dairy Sci, 2025, S0022-0302(25)00833-1 PLoS One, 2021, 16(5):e0252541
E4432	3,3-Dimethyl-1-butanol	3,3-Dimethyl-1-butanol (Neohexanol) is an orally active inhibitor of trimethylamine (TMA) and trimethylamine N-oxide (TMAO). 3,3-dimethyl-1-butanol negatively inhibits the signalling pathways of p65 NF-κB and TGF-β1/Smad3. 3,3-dimethyl-1-butanol has potential applications in cardiovascular disease (CVD).
S0752	AUDA	AUDA (compound 43) is a potent inhibitor of soluble epoxide hydrolase (sEH) with IC50 of 18 nM and 69 nM for the mouse sEH and human sEH, respectively. This compound has anti-inflammatory activity that reduces the protein expression of MMP-9, IL-1β, TNF-α and TGF-β. It downregulates Smad3 and p38 signaling pathways.
E0769	Ginsenoside Rh4	Ginsenoside Rh4 is an important active ingredient of traditional Chinese medicine ginseng, which has been shown to inhibit Wnt/β-Catenin, JAK2/STAT3, TGF-β/Smad2/3 and other signaling pathways.
S6807	TA-02	TA-02 is a p38 MAPK inhibitor with IC50 of 20 nM. This compound especially inhibits TGFBR-2.