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 (275)
Related Products (275)
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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.: 2926610-43-5
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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.
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PROTAC CDK4/6/9 degrader 1 prodrug
0 ImagesCat. No.: HY-178516PROTAC CDK4/6/9 degrader 1 prodrug is an orally active CDK4/CDK6/CDK9 PROTAC degrader prodrug. PROTAC CDK4/6/9 degrader 1 prodrug converts into PROTAC CDK4/6/9 degrader 1 (HY-178452). PROTAC CDK4/6/9 degrader 1 degrades CDK4, CDK6 and CDK9. PROTAC CDK4/6/9 degrader 1 prodrug is applicable to the research of triple-negative breast cancer (prodrug modification moiety: Lauric acid (HY-Y0366); PROTAC moiety: PROTAC CDK4/6/9 degrader 1 (HY-178452)).
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XYD129
0 ImagesCat. No.: HY-161710XYD129 is a CBP/p300 PROTAC degrader. XYD129 potently binds to CBP, p300 and CRBN proteins, with IC50 values of 0.021 μM, 0.03 μM and 0.18 μM, respectively. XYD129 forms a ternary CRBN-CBP/p300 complex and induces CBP/p300 degradation via the ubiquitin-proteasome system. XYD129 inhibits tumor growth and suppresses the proliferation of acute myeloid leukemia cells. XYD129 can be used in studies related to acute myeloid leukemia.
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PROTAC KSP degrader 1
0 ImagesCat. No.: HY-168725CAS No.: 3099825-86-9PROTAC KSP degrader 1 is a KSP PROTAC degrader with a DC50 of 114.8 nM. PROTAC KSP degrader 1 induces ubiquitination and degradation of KSP protein. PROTAC KSP degrader 1 induces G2/M phase arrest of the cell cycle. PROTAC KSP degrader 1 triggers Apoptosis. PROTAC KSP degrader 1 exhibits anticancer activity against colon cancer. PROTAC KSP degrader 1 can be used for the research of colon cancer, lung cancer and breast cancer.
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PROTAC AR Degrader-13
0 ImagesCat. No.: HY-184195PROTAC AR Degrader-13 is a proteolysis-targeting chimera (PROTACs) that targets the androgen receptor (AR). PROTAC AR Degrader-13 has a DC50 of 0.90 nM in LNCaP cells and a DC50 of 0.23 nM in hDPC cells. PROTAC AR Degrader-13 induces AR degradation, downregulates TGF-β1 expression, upregulates β-catenin levels, and restores the Wnt/β-catenin pro-proliferation signaling in hair follicles. In a testosterone-induced androgenetic alopecia mouse model, PROTAC AR Degrader-13 accelerates hair regeneration rate, increases hair density and hair diameter. PROTAC AR Degrader-13 can be used for the research of androgenetic alopecia.
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M9101
0 ImagesCat. No.: HY-184193M9101 is a selective Aurora A PROTAC degrader with a DC50 of 2.3 nM. M9101 induces G2/M arrest in triple-negative breast cancer cells and potently inhibits the proliferation of multiple tumor cell lines. M9101 can be used in the research of various cancers including triple-negative breast cancer.
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WB156
0 ImagesCat. No.: HY-174266CAS No.: 2368944-44-7WB156 is a dual MDM2 and GSPT1 PROTAC degrader with a DC50 of 23 nM against MDM2. WB156 induces the degradation of MDM2 and GSPT1 via the ubiquitin-proteasome system. WB156 upregulates the levels of p53 and p21, and triggers Apoptosis through the cleavage of PARP and Caspase-3. WB156 can be used in leukemia-related research.
