Cereblon
Cereblon (CRBN) functions as the substrate receptor of the CRL4 E3 ubiquitin ligase, mediating protein ubiquitination and degradation[1]. Mechanistically, CRBN regulates the Wnt signaling pathway by targeting Casein kinase 1α (CK1α), a negative regulator of β-Catenin, for degradation[1]. This Wnt-dependent modulation of CRBN influences developmental and disease-relevant phenotypes in zebrafish and Drosophila models[1]. Clinically, CRBN mutations have been identified in multiple myeloma patients with extramedullary disease, conferring resistance to immunomodulatory drugs (IMiDs) and highlighting its role in drug responsiveness[2]. Notably, these mutations include a Q99 truncating mutation and an R283K point mutation, impairing CRBN-mediated anti-myeloma activity[2]. Compared with related ubiquitin ligase substrate receptors, CRBN exhibits unique specificity for neo-substrates under both IMiD-bound and unbound conditions, distinguishing its functional isoform-dependent effects[1][2]. CRBN-targeted agonists, including IMiDs, exploit this substrate specificity to induce selective protein degradation, providing a basis for experimental modulation of Wnt and cancer-related pathways[1][2]. Therefore, CRBN serves as a central regulator of ubiquitin-mediated proteostasis, bridging signal transduction, disease pathophysiology, and therapeutic interventions[1][2].
References:
- [1]. Shen C, et al. The E3 ubiquitin ligase component, Cereblon, is an evolutionarily conserved regulator of Wnt signaling. Nat Commun. 2021 Sep 6;12(1):5263. [Content Brief]
- [2]. Egan JB, et al. Extramedullary myeloma whole genome sequencing reveals novel mutations in Cereblon, proteasome subunit G2 and the glucocorticoid receptor in multi drug resistant disease. Br J Haematol. 2013 Jun;161(5):748-751. [Content Brief]
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Cereblon Related Products (277)
Related Products (277)
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GSK699
0 ImagesGSK699 is a KAT2A/B/PCAF/GCN5 PROTAC degrader. GSK699 induces proteasome-dependent degradation of KAT2A, KAT2B, PCAF and GCN5, regulates the histone acetyltransferase activity of the SAGA complex, and reduces the level of histone H3K9ac. GSK699 inhibits the growth of neuroblastoma, acute myeloid leukemia and small cell lung cancer cells. GSK699 reduces the production of inflammatory cytokines and chemokines, and impairs LPS-stimulated immune cell responses. GSK699 is applicable to research related to acute myeloid leukemia, small cell lung cancer, neuroblastoma and inflammatory diseases.
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MT-802
0 ImagesMT-802 is a BTK PROTAC degrader. MT-802 degrades wild-type BTK (DC50 = 14.6 nM) and BTK mutants including E41K, C481S (DC50 = 14.9 nM), C481R, C481Y, C481T, C481F, L528W, and inhibits their Y223 phosphorylation. BI-4732 can be used for the study of Ibrutinib (HY-10997)-resistant chronic lymphocytic leukemia (CLL). (Pink: BTK ligand (HY-150885), Blue: CRBN Ligand (HY-14658), Black: Linker (HY-141371), E3 ligase ligand-linker conjugate (HY-176340)).
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PROTAC BTK Degrader-1
0 ImagesPROTAC BTK Degrader-1 is a selective, orally active BTK PROTAC degrader with a DC50 of 5.8 nM. PROTAC BTK Degrader-1 induces ubiquitination and degradation of wild-type and mutant (C481S, T316) BTK proteins via the CRBN-mediated pathway. PROTAC BTK Degrader-1 exhibits anticancer activity against diffuse large B-cell lymphoma. PROTAC BTK Degrader-1 can be used in lymphoma-related research.
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SD-436
0 ImagesSD-436 is a highly selective and efficacious STAT3 PROTAC degrader (DC50: 0.5 μM), with IC50 of 19 nM (STAT3), 270 nM (STAT1), 360 nM (STAT4), >10 μM (STAT5) and >10 μM (STAT6). SD-436 promotes ubiquitination and degradation of STAT3, and induces tumor regression. SD-436 can be used for tumor research, such as leukemia and lymphoma.
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BI-3663
0 ImagesBI-3663 is a highly selective PTK2/FAK PROTAC (DC50 = 30 nM) with a Cereblon E3 ligase ligand capable of degrading PTK2, with an IC50 value of 18 nM. BI-3663 is a PROTAC generated by linking the PTK2/FAK inhibitor BI-4464 (HY-124625) with a Pomalidomide (HY-10984) derivative via a linker. BI-3663 can induce PTK2 degradation at low nanomolar concentrations. BI-3663 has antitumor activity.
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GBD-9
0 ImagesGBD-9 is a degrader based on the E3 ubiquitin ligase CRBN that targets BTK and the G1 to S phase transition protein GSPT1. GBD-9 has both PROTAC and molecular glue properties by inducing ubiquitination and proteasomal degradation of target proteins. GBD-9 can efficiently degrade wild-type and mutant BTK (such as C481S mutation) and GSPT1. GBD-9 significantly inhibits tumor cell proliferation by inducing G1 phase arrest in cancer cells, downregulating anti-apoptotic proteins (BCL-2, MCL-1) and activating Caspase-3 to induce apoptosis. GBD-9 is mainly used in the research of hematological tumors such as diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML).
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PROTAC JAK1 degrader 1
0 ImagesPROTAC JAK1 degrader 1 is a JAK1 PROTAC degrader with a DC50 of 214 nM and an IC50 of 5.2 nM. PROTAC JAK1 degrader 1 inhibits the downstream JAK-STAT signaling pathway by degrading JAK1. PROTAC JAK1 degrader 1 exhibits antiproliferative activity in cells. PROTAC JAK1 degrader 1 can be used for research on leukemia.
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PROTAC EGFR degrader 9
0 ImagesPROTAC EGFR degrader 9 (Compound C6) is an orally active CRBN-based PROTAC EGFR degrader. PROTAC EGFR degrader 9 exhibits a DC50 of 10.2 nM and a Kd of 240.2 nM against EGFRL858R/T790M/C797S. PROTAC EGFR degrader 9 exhibits potent degradation activity against various EGFR mutants, while sparing the EGFRWT. (Blue: CRBN ligand (HY-A0003), Black: linker (HY-161613); Pink: EGFR inhibitor (HY-161537)).
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PROTAC PD-1/PD-L1 degrader-1
0 ImagesPROTAC PD-1/PD-L1 degrader-1, a PD-1/PD-L1 PROTAC based on Cereblon E3 ligand, inhibits PD-1/PD-L1 interaction with an IC50 of 39.2 nM. PROTAC PD-1/PD-L1 degrader-1 significantly restores the immunity repressed in a co-culture model of Hep3B/OS-8/hPD-L1 and CD3 T cells. PROTAC PD-1/PD-L1 degrader-1 moderately reduces the protein levels of PD-L1 in a lysosome-dependent manner.
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ZLC491
0 ImagesZLC491 is an orally active PROTAC degrader that selectively targets CDK12/CDK13 and exhibits certain oral bioavailability. ZLC491 induces cereblon- and proteasome-dependent selective degradation of CDK12 and CDK13. ZLC491 inhibits the transcription and expression of long genes, and mainly acts on a subset of DNA damage response genes. ZLC491 inhibits the proliferation of various triple-negative breast cancer cells. ZLC491 can be used in research related to triple-negative breast cancer.
