E3 Ligase
Signaling Pathway Map
Research Area
Inhibitory Selectivity
E3 Ligase Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1029 |
Lenalidomide (CC-5013)Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM in PBMCs. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide promotes cleaved caspase-3 expression and inhibit VEGF expression and induces apoptosis. |
Effect of lenalidomide treatment (50 mg/kg/day, p.o. for 3 days) on expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Fas, Fas ligand (FasL), and cleaved caspase-3 in myocardium from lean and ob/ob mice. (a) Representative gel blots of TNF-α, IL-6, Fas, FasL, cleaved caspase-3 and α-Tubulin (as loading control) using specific antibodies. (b) TNF-α. |
|
| S1567 |
PomalidomidePomalidomide (CC-4047) inhibits LPS-induced TNF-α release with IC50 of 13 nM in PBMCs. Pomalidomide can be utilized in PROTAC as a ligand for targeting E3 ligase and inhibiting the E3 ligase protein cereblon (CRBN). Pomalidomide promotes apoptosis and cell cycle arrest. |
OPM2 cells stably expressing either NT or CRBN shRNA were seeded and incubated with pomalidomide at the indicated concentration, followed by MTT assay at day 3 after adding drugs. Each experimental condition was performed in triplicate and repeated at least once.
|
|
| S1193 |
ThalidomideThalidomide was introduced as a sedative drug, immunomodulatory agent and also is investigated for treating symptoms of many cancers. Thalidomide inhibits an E3 ubiquitin ligase, which is a CRBN-DDB1-Cul4A complex. |
(E) MM.1S cells were treated with Thal(Thalidomide) or Pom for 48 hours. In each case, western blot was carried out using cell lysates and the indicated Abs.
|
|
| S9724New |
SZL P1-41SZL P1-41 (compound #25) is a specific inhibitor of S-phase kinase-associated protein 2 (Skp2) that indeed binds to Skp2, prevents Skp2-Skp1 interaction and inhibits Skp2 SCF E3 ligase activity, which consequently suppresses survival of cancer cells and cancer stem cells. SZL P1-41 causes higher apoptosis rates in cancer cells. |
||
| S8449New |
VH298VH298 is a potent VHL (Von Hippel-Lindau, the E3 ligase) inhibitor that stabilizes HIF-α. VH298 blocks the VHL:HIF-α interaction with Kd of 90 nM in isothermal titration calorimetry (ITC) and 80 nM in a competitive fluorescence polarization assay. VH-298 can be used in PROTAC technology. |
||
| S8979New |
THAL-SNS-032THAL-SNS-032 is a selective Cyclin-dependent kinase 9 (CDK9) degrader PROTAC consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative that binds the E3 ubiquitin ligase Cereblon (CRBN). |
||
| S9605New |
ApcinApcin (APC inhibitor) is an inhibitor of the E3 ligase activity of the mitotic anaphase-promoting complex/cyclosome (APC/C) that binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. |
||
| S2225 |
TAMETosyl-L-Arginine Methyl Ester (TAME) is an APC inhibitor. |
Knockdown of p21 or inhibiting APC/C by TAME sensitized NSCLC cells to 5-FU. Cells were treated with 5-FU. 2 days after treatment, surviving cells were stained with cystal violet. Representive microscopic fields were shown. The blue stained cells were counted and shown in histogram at the right side.
|
|
| S2781 |
RITA (NSC 652287)RITA (NSC 652287) induces both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks, and also inhibits MDM2-p53 interaction by targeting p53. |
To determine the number of viable cells, cells were serum starved for 8 hours and treated with 25 nM RITA and stimulated with 1ug/mL SDF1α for 48 hours in serum-free media. After 48 hours, cells were harvested and counted by trypan blue exclusion, using standard methods.
|
|
| 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. |
G, cells treated with the SM406 (1 μmol/L) for 48 hours were subjected to Western blotting. |
|
| S5315 |
PRT4165PRT4165 is a Bmi1/Ring1A inhibitor with an IC50 of 3.9 µM in the cell-free assay and also inhibits PRC1-mediated H2A ubiquitylation in vivo and in vitro. |
||
| S8760 |
Iberdomide (CC220)Iberdomide (CC-220) is a novel oral immunomodulatory compound that targets cereblon, part of the CRL4CRBN E3 ubiquitin ligase complex, with an IC50 of 60 nM in a competitive TR-FRET assay. Iberdomide (CC-220) induces apoptosis with antitumor and immunostimulatory activities. |
||
| S7892 |
Avadomide (CC-122)Avadomide (CC-122), a new chemical entity termed pleiotropic pathway modifier, is a novel agent for Diffuse large B-cell lymphoma(DLBCL) with antitumor and immunomodulatory activity. Its molecular target is the protein cereblon (CRBN), a substrate receptor of the cullin ring E3 ubiquitin ligase complex CRL4CRBN. |
||
| S0095 |
VL285VL285 is a potent VHL ligand that degrades HaloTag7 fusion proteins. Cotreatment with excess VL285, the core VHL ligand from which HaloPROTAC3 is derived, is able to significantly reduce HaloPROTAC3 mediated activity to 50% degradation. |
||
| S0097 |
(S,R,S)-AHPC (MDK7526)(S,R,S)-AHPC (MDK7526, VH032-NH2, VHL ligand 1) is the VH032-based VHL ligand used in the recruitment of the von Hippel-Lindau (VHL) protein. (S,R,S)-AHPC is potential useful for the targeted degradation of the androgen receptor. (S,R,S)-AHPC can be connected to the ligand for protein such as BCR-ABL1 by a linker to form PROTACs such as GMB-475. GMB-475 induces the degradation of BCR-ABL1 with IC50 of 1.11 μM in Ba/F3 cells. |
||
| S8652 |
Skp2 inhibitor C1 (SKPin C1)Skp2 inhibitor C1 (SKPin C1) is a specific and selective small-molecule inhibitor of Skp2-mediated p27 degradation by reducing p27 binding through key compound-receptor contacts. |
||
| S2678 |
NSC 207895NSC 207895 (XI-006) suppresses MDMX with IC50 of 2.5 μM, leading to enhanced p53 stabilization/activation and DNA damage, and also regulates MDM2, an E3 ligase. |
Median overall survival of mice (n = 5 mice in vehicle and PYR-41; n = 4 mice in NSC group) inoculated with IOWA-1T xenografts were increased to 43 ± 0.5 and 39 ± 2 days with PYR-41 (PYR) and NSC-207895 (NSC), respectively, compared with a vehicle-treated control group 33 ± 1 days (*p < 0.05).
|
|
| S1061 |
Nutlin-3Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM in a cell-free assay; stabilizes p73 in p53-deficient cells. |
Ubiquitination of p53 in vivo by BIRC6 in the presence of Nutlin-3. Cells were treated with Nutlin-3 (20 uM, 24 h) before harvest. Cell lysates were immunoprecipitated with anti-p53 antibody and immunoblotted by anti-ubiquitin antibody.
|
|
| S1172 |
JNJ-26854165 (Serdemetan)JNJ-26854165 (Serdemetan) acts as a HDM2 ubiquitin ligase antagonist and also induces early apoptosis in p53 wild-type cells, inhibits cellular proliferation followed by delayed apoptosis in the absence of functional p53. Phase 1. |
|
|
| S8975New |
CC-92480CC-92480 is a novel protein degrader and a cereblon E3 ligase modulator (CELMoD) that has anti-myeloma activity. |
||
| S3502New |
(S,R,S)-AHPC-PEG4-NH2 hydrochloride(S,R,S)-AHPC-PEG4-NH2 hydrochloride (VH032-PEG4-NH2 hydrochloride, VHL Ligand-Linker Conjugates 4 hydrochloride, E3 ligase Ligand-Linker Conjugates 7) is a PROTAC E3 ligase ligand-linker conjugate that incorporates the (S,R,S)-AHPC based VHL ligand and 4-unit PEG linker. |
||
| S8888 |
GMB-475GMB-475 is a proteolysis-targeting chimera (PROTAC) that allosterically targets BCR-ABL1 protein and recruit the E3 ligase Von Hippel-Lindau (VHL), resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein. |
||
| S6794 |
Thalidomide-O-COOH (Cereblon ligand 3)Thalidomide-O-COOH (Cereblon ligand 3, E3 ligase Ligand 3), a Thalidomide-based Cereblon (CRBN) ligand, is used in the recruitment of CRBN protein. Thalidomide-O-COOH (Cereblon ligand 3) can be connected to the ligand for protein by a linker to form PROTACs (Proteolysis Targeting Chimera). |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1029 |
Lenalidomide (CC-5013)Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM in PBMCs. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide promotes cleaved caspase-3 expression and inhibit VEGF expression and induces apoptosis. |
Effect of lenalidomide treatment (50 mg/kg/day, p.o. for 3 days) on expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Fas, Fas ligand (FasL), and cleaved caspase-3 in myocardium from lean and ob/ob mice. (a) Representative gel blots of TNF-α, IL-6, Fas, FasL, cleaved caspase-3 and α-Tubulin (as loading control) using specific antibodies. (b) TNF-α. |
|
| S1567 |
PomalidomidePomalidomide (CC-4047) inhibits LPS-induced TNF-α release with IC50 of 13 nM in PBMCs. Pomalidomide can be utilized in PROTAC as a ligand for targeting E3 ligase and inhibiting the E3 ligase protein cereblon (CRBN). Pomalidomide promotes apoptosis and cell cycle arrest. |
OPM2 cells stably expressing either NT or CRBN shRNA were seeded and incubated with pomalidomide at the indicated concentration, followed by MTT assay at day 3 after adding drugs. Each experimental condition was performed in triplicate and repeated at least once.
|
|
| S1193 |
ThalidomideThalidomide was introduced as a sedative drug, immunomodulatory agent and also is investigated for treating symptoms of many cancers. Thalidomide inhibits an E3 ubiquitin ligase, which is a CRBN-DDB1-Cul4A complex. |
(E) MM.1S cells were treated with Thal(Thalidomide) or Pom for 48 hours. In each case, western blot was carried out using cell lysates and the indicated Abs.
|
|
| S9724New |
SZL P1-41SZL P1-41 (compound #25) is a specific inhibitor of S-phase kinase-associated protein 2 (Skp2) that indeed binds to Skp2, prevents Skp2-Skp1 interaction and inhibits Skp2 SCF E3 ligase activity, which consequently suppresses survival of cancer cells and cancer stem cells. SZL P1-41 causes higher apoptosis rates in cancer cells. |
||
| S8449New |
VH298VH298 is a potent VHL (Von Hippel-Lindau, the E3 ligase) inhibitor that stabilizes HIF-α. VH298 blocks the VHL:HIF-α interaction with Kd of 90 nM in isothermal titration calorimetry (ITC) and 80 nM in a competitive fluorescence polarization assay. VH-298 can be used in PROTAC technology. |
||
| S8979New |
THAL-SNS-032THAL-SNS-032 is a selective Cyclin-dependent kinase 9 (CDK9) degrader PROTAC consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative that binds the E3 ubiquitin ligase Cereblon (CRBN). |
||
| S9605New |
ApcinApcin (APC inhibitor) is an inhibitor of the E3 ligase activity of the mitotic anaphase-promoting complex/cyclosome (APC/C) that binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. |
||
| S2225 |
TAMETosyl-L-Arginine Methyl Ester (TAME) is an APC inhibitor. |
Knockdown of p21 or inhibiting APC/C by TAME sensitized NSCLC cells to 5-FU. Cells were treated with 5-FU. 2 days after treatment, surviving cells were stained with cystal violet. Representive microscopic fields were shown. The blue stained cells were counted and shown in histogram at the right side.
|
|
| S2781 |
RITA (NSC 652287)RITA (NSC 652287) induces both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks, and also inhibits MDM2-p53 interaction by targeting p53. |
To determine the number of viable cells, cells were serum starved for 8 hours and treated with 25 nM RITA and stimulated with 1ug/mL SDF1α for 48 hours in serum-free media. After 48 hours, cells were harvested and counted by trypan blue exclusion, using standard methods.
|
|
| 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. |
G, cells treated with the SM406 (1 μmol/L) for 48 hours were subjected to Western blotting. |
|
| S5315 |
PRT4165PRT4165 is a Bmi1/Ring1A inhibitor with an IC50 of 3.9 µM in the cell-free assay and also inhibits PRC1-mediated H2A ubiquitylation in vivo and in vitro. |
||
| S8760 |
Iberdomide (CC220)Iberdomide (CC-220) is a novel oral immunomodulatory compound that targets cereblon, part of the CRL4CRBN E3 ubiquitin ligase complex, with an IC50 of 60 nM in a competitive TR-FRET assay. Iberdomide (CC-220) induces apoptosis with antitumor and immunostimulatory activities. |
||
| S7892 |
Avadomide (CC-122)Avadomide (CC-122), a new chemical entity termed pleiotropic pathway modifier, is a novel agent for Diffuse large B-cell lymphoma(DLBCL) with antitumor and immunomodulatory activity. Its molecular target is the protein cereblon (CRBN), a substrate receptor of the cullin ring E3 ubiquitin ligase complex CRL4CRBN. |
||
| S0095 |
VL285VL285 is a potent VHL ligand that degrades HaloTag7 fusion proteins. Cotreatment with excess VL285, the core VHL ligand from which HaloPROTAC3 is derived, is able to significantly reduce HaloPROTAC3 mediated activity to 50% degradation. |
||
| S0097 |
(S,R,S)-AHPC (MDK7526)(S,R,S)-AHPC (MDK7526, VH032-NH2, VHL ligand 1) is the VH032-based VHL ligand used in the recruitment of the von Hippel-Lindau (VHL) protein. (S,R,S)-AHPC is potential useful for the targeted degradation of the androgen receptor. (S,R,S)-AHPC can be connected to the ligand for protein such as BCR-ABL1 by a linker to form PROTACs such as GMB-475. GMB-475 induces the degradation of BCR-ABL1 with IC50 of 1.11 μM in Ba/F3 cells. |
||
| S8652 |
Skp2 inhibitor C1 (SKPin C1)Skp2 inhibitor C1 (SKPin C1) is a specific and selective small-molecule inhibitor of Skp2-mediated p27 degradation by reducing p27 binding through key compound-receptor contacts. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S2678 |
NSC 207895NSC 207895 (XI-006) suppresses MDMX with IC50 of 2.5 μM, leading to enhanced p53 stabilization/activation and DNA damage, and also regulates MDM2, an E3 ligase. |
Median overall survival of mice (n = 5 mice in vehicle and PYR-41; n = 4 mice in NSC group) inoculated with IOWA-1T xenografts were increased to 43 ± 0.5 and 39 ± 2 days with PYR-41 (PYR) and NSC-207895 (NSC), respectively, compared with a vehicle-treated control group 33 ± 1 days (*p < 0.05).
|
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1061 |
Nutlin-3Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM in a cell-free assay; stabilizes p73 in p53-deficient cells. |
Ubiquitination of p53 in vivo by BIRC6 in the presence of Nutlin-3. Cells were treated with Nutlin-3 (20 uM, 24 h) before harvest. Cell lysates were immunoprecipitated with anti-p53 antibody and immunoblotted by anti-ubiquitin antibody.
|
|
| S1172 |
JNJ-26854165 (Serdemetan)JNJ-26854165 (Serdemetan) acts as a HDM2 ubiquitin ligase antagonist and also induces early apoptosis in p53 wild-type cells, inhibits cellular proliferation followed by delayed apoptosis in the absence of functional p53. Phase 1. |
|
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S8975New |
CC-92480CC-92480 is a novel protein degrader and a cereblon E3 ligase modulator (CELMoD) that has anti-myeloma activity. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S3502New |
(S,R,S)-AHPC-PEG4-NH2 hydrochloride(S,R,S)-AHPC-PEG4-NH2 hydrochloride (VH032-PEG4-NH2 hydrochloride, VHL Ligand-Linker Conjugates 4 hydrochloride, E3 ligase Ligand-Linker Conjugates 7) is a PROTAC E3 ligase ligand-linker conjugate that incorporates the (S,R,S)-AHPC based VHL ligand and 4-unit PEG linker. |
||
| S8888 |
GMB-475GMB-475 is a proteolysis-targeting chimera (PROTAC) that allosterically targets BCR-ABL1 protein and recruit the E3 ligase Von Hippel-Lindau (VHL), resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein. |
||
| S6794 |
Thalidomide-O-COOH (Cereblon ligand 3)Thalidomide-O-COOH (Cereblon ligand 3, E3 ligase Ligand 3), a Thalidomide-based Cereblon (CRBN) ligand, is used in the recruitment of CRBN protein. Thalidomide-O-COOH (Cereblon ligand 3) can be connected to the ligand for protein by a linker to form PROTACs (Proteolysis Targeting Chimera). |
