ZXH-4-137
ZXH-4-137 is a CRBN PROTAC degrader. ZXH-4-137 brings CRBN and VHL E3 ligase into proximity, induces CRBN ubiquitination and proteasomal degradation, and exhibits high selectivity for CRBN. ZXH-4-137 blocks the degradation of CRBN-dependent target proteins such as GSPT1 and CDK9. ZXH-4-137 serves as a chemical knockdown tool compound for investigating CRBN-dependent biological processes.
(Pink: Cereblon ligand (HY-103596); Blue: VHL ligand (HY-112078); Black: linker (HY-132859)).
For research use only. We do not sell to patients.
- CAS No.: 2711006-74-3
- Formula: C47H60N6O9S
- Molecular Weight:885.08
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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Cereblon |
VHL |
ZXH-4-137 (10-500 nM; 1-24 h) potently and selectively induces CRBN degradation in MM1.S cells[1].
ZXH-4-137 (50 nM; 2 h pre-treatment) mediates the knockdown of CRBN in MM1.S cells, and this effect blocks the CRBN-dependent degradation of GSPT1 by CC-885 (HY-101488)[1].
Knockdown of CRBN in MOLT-4 cells mediated by ZXH-4-137 (0.1 μM; 2 h pre-treatment) partially blocks the CRBN-dependent degradation of CDK9 induced by THAL-SNS-032 (HY-123937)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MM1.S multiple myeloma cells
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Concentration:10 nM, 50 nM, 100 nM, 500 nM
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Incubation Time:4 h
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Result:Reduced CRBN levels to 44% of DMSO control at 10 nM, 31% at 50 nM, 16% at 100 nM, and 17% at 500 nM after 4 hours.
Did not significantly alter levels of Ikaros, Aiolos, CK1α, pVHL30, or pVHL19 at any tested concentration.
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Cell Line:MM1.S multiple myeloma cells
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Concentration:50 nM
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Incubation Time:1 h, 2 h, 4 h, 8 h, 16 h, 24 h
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Result:Reduced CRBN levels to 58% of DMSO control at 1 h, 41% at 2 h, 23% at 4 h, 17% at 8 h, 13% at 16 h, and 31% at 24 h.
Left levels of Ikaros, pVHL30, and pVHL19 largely unchanged across all time points.
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Cell Line:MM1.S multiple myeloma cells
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Concentration:50 nM (ZXH-4-137 pre-treatment); 0.1 μM (CC-885)
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Incubation Time:2 h (ZXH-4-137 pre-treatment); 4 h (CC-885 incubation)
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Result:Rescued CC-885-induced GSPT1 degradation, maintaining GSPT1 levels comparable to DMSO control.
Induced nearly complete CRBN degradation.
Achieved rescue comparable to that seen with proteasome inhibitor carfilzomib pre-treatment.
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Cell Line:MOLT-4 leukemia cells
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Concentration:0.1 μM (ZXH-4-137 pre-treatment); 0.25 μM (THAL-SNS-032)
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Incubation Time:2 h (ZXH-4-137 pre-treatment); 6 h (THAL-SNS-032 incubation)
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Result:Partially prevented THAL-SNS-032-induced CDK9 degradation.
Induced nearly complete CRBN degradation.
Achieved partial rescue more effective than pre-treatment with 0.1 μM Pomalidomide.
Chemical Information
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CAS No. 2711006-74-3
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Molecular Weight 885.08
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Formula C47H60N6O9S
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SMILES
O=C1C2=C(OCCCCCCCCCCC(N[C@@H](C(C)(C)C)C(N3[C@@H](C[C@H](C3)O)C(N[C@H](C4=CC=C(C5=C(N=CS5)C)C=C4)C)=O)=O)=O)C=CC=C2C(N1C6C(NC(CC6)=O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ZXH-4-137 Related Classifications
HY-132862 Related Classifications
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