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 (281)
Related Products (281)
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MS9117
0 ImagesCat. No.: HY-184097CAS No.: 3098670-37-9MS9117 is a PROTAC molecule that targets and degrades LSD1/BHC110 by recruiting CRBN. MS9117 effectively increases the level of histone H3 lysine 4 monomethylation. MS9117 significantly inhibits the proliferation and colony formation of cancer cells, promotes their myeloid differentiation, and enhances the sensitivity of non-acute promyelocytic leukemia-type AML cells to all-trans retinoic acid (ATRA).
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UNC8461
0 ImagesCat. No.: HY-183100UNC8461 is a PROTAC and is negative control CRBN-recruiting PROTAC analog of UNC8209 (HY-183098). UNC8461 features a methyl group substitution on its CRBN ligand to disrupt CRBN binding. UNC8461 fails to reduce TBK1, AAK1, GAK, and AURKA protein levels in renal cancer cells. UNC8461 does not suppress 3-D soft agar colony formation in renal cancer cells, and exerts modest, partial inhibition on colony formation in some renal cancer cells.
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IHMT-BMX-068
0 ImagesCat. No.: HY-184005IHMT-BMX-068 is a BMX PROTAC degrader with a DC50 of 0.007 μM. IHMT-BMX-068 promotes ubiquitination and degradation of BMX. IHMT-BMX-068 increases the levels of cleaved PARP and cleaved Caspase-3, and induces Apoptosis. IHMT-BMX-068 exerts anti-cancer effects against prostate cancer. IHMT-BMX-068 can be used for the research of prostate cancer.
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PROTAC HPK1 Degrader-8
0 ImagesCat. No.: HY-184230CAS No.: 3120899-50-2PROTAC HPK1 Degrader-8 is a HPK1 PROTAC degrader with a DC50 of 1-10 nM. PROTAC HPK1 Degrader-8 promotes HPK1 ubiquitination and degradation. PROTAC HPK1 Degrader-8 induces IL-2 production, with an EC50 of 3 nM. PROTAC HPK1 Degrader-8 can be used in research related to hematologic malignancies and solid tumors.
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PROTAC SMARCA2 degrader-3
0 ImagesCat. No.: HY-162245CAS No.: 3024266-69-8PROTAC SMARCA2 degrader-3 is a PROTAC degrader of the SWI/SNF ATPase subunits, SMARCA2. PROTAC SMARCA2 degrader-3 has anticancer effects (WO2023244764A1; Compound 153).
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GSK702
0 ImagesCat. No.: HY-185009CAS No.: 2260944-69-0GSK702, a PROTAC, is a the less active cis-(S,S)-enantiomer of GSK983 (P300/CBP-associated factor (PCAF)/general control nonderepressible 5 (GCN5) PROTAC). GSK702 induces only a small decrease of PCAF protein levels. GSK702 binds to CRBN and causes a reduction of IL-1β in macrophages. GSK702 can be used for the study of inflammatory mediators.
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Abd141
0 ImagesCat. No.: HY-187195Abd141 is a dual PROTAC degrader of ATR and Aurora kinase A (AURKA), with DC50 values of 97.7 nM and 6.7 nM, respectively. Abd141 inhibits the proliferation of acute lymphoblastic leukemia cells. Abd141 can be used in the research of acute lymphoblastic leukemia.
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C9S
0 ImagesCat. No.: HY-184233C9S is an As (III)-PROTAC and arsenic-binding protein PROTAC degrader. C9S promotes the ubiquitination and degradation of arsenic-binding proteins such as Glutathione reductase. C9S binds to metallothionein. C9S exhibits anticancer activity against lung cancer. C9S can be used in lung cancer-related research.
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PROTAC K-Ras Degrader-6
0 ImagesCat. No.: HY-168678CAS No.: 3052745-46-4PROTAC K-Ras Degrader-6 (compound 102) is a potent cereblon-based KRAS PROTAC degrader, with a DC50 of ≤100 nM. PROTAC K-Ras Degrader-6 shows anticancer effects.
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Truly-4
0 ImagesCat. No.: HY-187439Truly-4 is a bifunctional Rpn13 PROTAC and CRBN ByeTAC degrader. Degradation of Rpn13 relies on CRBN-mediated E3 ubiquitin ligase activity, while degradation of CRBN itself proceeds via a ByeTAC mechanism of action. Truly-4 induces selective cytotoxicity in hematological cancer cells and solid cancer cells, but not in healthy cells, despite comparable levels of Rpn13 depletion in both cell types. Truly-4 can be used in studies related to B-cell lymphoma and triple-negative breast cancer.
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TQ-3959
0 ImagesCat. No.: HY-175541CAS No.: 2926610-43-5TQ-3959 is an orally active BTK PROTAC degrader, with a DC50 of 14.6 nM. TQ-3959 exerts antiproliferative activity against both wild-type BTK and C481S mutant BTK cell lines. TQ-3959 exhibits tumor growth inhibition in female NOD-SCID mice bearing TMD-8 xenografts. TQ-3959 can be used in the research on B-cell malignancies such as lymphoma.
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PD-305
0 ImagesCat. No.: HY-183937APD-305 is a selective PTPN2 PROTAC degrader, with DC50 values of 0.25 nM and 5.11 nM against PTPN2 and PTPN1, respectively. PD-305 enhances IFN-γ-induced STAT1 phosphorylation, inhibits the proliferation of IFN-γ-stimulated colorectal cancer cells, promotes CD8+ T cell activation, enhances the tumor-killing activity of T cells, and suppresses tumor growth in mouse models. PD-305 can be used for the research of colorectal cancer.
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PROTAC ATR degrader-3
0 ImagesCat. No.: HY-182016CAS No.: 3126270-11-6PROTAC ATR degrader-3 is a potent CRBN-based ATR PROTAC degrader with a DC50 of 127 nM. PROTAC ATR degrader-3 also degrades CHK1 with an DC50 of 135 nM. PROTAC ATR degrader-3 inhibits cancer cells proliferation, migration and invasion, triggers apoptosis and induces S phase arrest and DNA damage. PROTAC ATR degrader-3 achieves tumor growth inhibition in LoVo xenograft mouse model without apparent toxicity. PROTAC ATR degrader-3 can be used for the research of colorectal cancer.
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PROTAC EGFR degrader 17
0 ImagesCat. No.: HY-180917CAS No.: 3065209-64-2
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PROTAC SMARCA2 degrader-30
0 ImagesCat. No.: HY-168257CAS No.: 2408393-67-7
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PROTAC TSSK1 Degrader-1
0 ImagesCat. No.: HY-184428PROTAC TSSK1 Degrader-1 is a TSSK1 PROTAC degrader with a DC50 of 10.8 nM and an IC50 of 56.8 nM. PROTAC TSSK1 Degrader-1 reduces sperm motility and impairs in vitro fertilization capacity. PROTAC TSSK1 Degrader-1 undergoes metabolic N-dealkylation and exhibits high efflux properties. PROTAC TSSK1 Degrader-1 is applicable to studies related to male fertility.
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PROTAC ALK degrader-3
0 ImagesCat. No.: HY-168551PROTAC ALK degrader-3 is an orally active ALK PROTAC degrader with a DC50 of 119.33 nM in Karpas 299 cells. PROTAC ALK degrader-3 induces the degradation of ALK fusion proteins via the ubiquitin-proteasome system. PROTAC ALK degrader-3 induces NPM-ALK degradation and inhibits the expression of p-ALK and p-STAT3. PROTAC ALK degrader-3 inhibits cancer cell proliferation and suppresses the growth of xenografts in vivo. PROTAC ALK degrader-3 can be used for the research of ALK-positive cancers (e.g., anaplastic large cell lymphoma).
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PROTAC RET Degrader 2
0 ImagesCat. No.: HY-183783PROTAC RET Degrader 2 is a RET degrader with a target IC50 of 0.36 nM. PROTAC RET Degrader 2 is mainly composed of RET-IN-34 (HY-183729) and Thalidomide (HY-14658). PROTAC RET Degrader 2 mediates RET degradation via the ubiquitin-proteasome system. PROTAC RET Degrader 2 induces apoptosis, inhibits colony-forming ability, and exhibits antiproliferative activity in cancer cells. PROTAC RET Degrader 2 suppresses tumor growth in xenograft models. PROTAC RET Degrader 2 can be used in research related to medullary thyroid carcinoma, papillary thyroid carcinoma, and RET fusion-positive lung adenocarcinoma.
