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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PROTAC PI3Kα/δ degrader-1
0 ImagesCat. No.: HY-182083PROTAC PI3Kα/δ degrader-1 is an orally active PI3Kα/δ PROTAC degrader, with an IC50 of 0.34 nM for PI3Kα and 1.85 nM for PI3Kδ. PROTAC PI3Kα/δ degrader-1 inhibits the proliferation and migration of cancer cells, induces G1-phase cell cycle arrest and PI3Kα degradation. PROTAC PI3Kα/δ degrader-1 suppresses tumor growth in breast cancer xenograft mouse models. PROTAC PI3Kα/δ degrader-1 can be used for the research of breast cancer.
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PROTAC HDAC8 Degrader-4
0 ImagesCat. No.: HY-181024PROTAC HDAC8 Degrader-3 (Compound BP6) is an efficient, selective and low-toxicity HDAC8 PROTAC degrader with a DC50 of 80 nM. PROTAC HDAC8 Degrader-3 exhibits IC50 of PROTAC for HDAC8 and CRBN of 0.26 and 30 μM respectively. PROTAC HDAC8 Degrader-3 increases the level of Ac-SMC3, stabilizes p53 and sensitizes targeted reagents (such as Idasanutlin (HY-15676)), demonstrating its great potential in combination therapy.
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PROTAC BRD2/BRD4 degrader-1
0 ImagesCat. No.: HY-130612CAS No.: 2570470-42-5PROTAC BRD2/BRD4 degrader-1 (compound 15) is a potent and selective BET protein BRD4 and BRD2 degrader, connected by ligands for Cereblon and BET. PROTAC BRD2/BRD4 degrader-1 rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 and BRD2 over BRD3. PROTAC BRD2/BRD4 degrader-1 effectively inhibits solid tumors with low cytotoxic effect.
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PROTAC FAK degrader 3
0 ImagesCat. No.: HY-175459PROTAC FAK degrader 3 is a potent and selective FAK PROTAC degrader with a DC50 of 1.08 nM. PROTAC FAK degrader 3 induces the ubiquitination and proteasomal degradation of FAK by binding to CRBN, thereby blocking oncogenic signaling, specifically upregulating MHC-I to enhance antigen presentation, and subsequently activating CD8+ T cell-mediated antitumor immune responses. PROTAC FAK degrader 3 can be used in related research on hepatocellular carcinoma, ovarian cancer, and breast cancer.
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PROTAC FLT-3 degrader 4
0 ImagesCat. No.: HY-158325CAS No.: 2956722-48-6PROTAC FLT-3 degrader 4 is an orally active CRBN-based FLT3-PROTAC degrader that potently induces FLT3-ITD degradation through the ubiquitin-proteasome system. PROTAC FLT-3 degrader 4 shows highly selective to FLT3-ITD mutant acute myeloid leukemia (AML) cells. (Blue: CRBN ligand, Black: linker; Pink: FLT3 inhibitor).
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PROTAC METTL3-14 degrader 1
0 ImagesCat. No.: HY-162282CAS No.: 3039554-79-2PROTAC METTL3-14 degrader 1 is a METTL3-METTL14 heterodimer complex PROTAC degrader. PROTAC METTL3-14 degrader 1 binds to the E3 ubiquitin ligase CRBN, forms a ternary complex with METTL3-METTL14, and promotes the ubiquitination and degradation of METTL3. PROTAC METTL3-14 degrader 1 is applicable to the research of acute myeloid leukemia and prostate cancer.
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PROTAC YTHDC1 Degrader-1
0 ImagesCat. No.: HY-184495PROTAC YTHDC1 Degrader-1 is a selective, CRBN-recruiting YTHDC1 PROTAC degrader with a DC50 of 11.42 nM. PROTAC YTHDC1 Degrader-1 induces ubiquitination and degradation of YTHDC1. PROTAC YTHDC1 Degrader-1 induces G1 phase arrest and inhibits cell cycle progression. PROTAC YTHDC1 Degrader-1 also induces Apoptosis. PROTAC YTHDC1 Degrader-1 exhibits anticancer activity against leukemia. PROTAC YTHDC1 Degrader-1 can be used for the research of acute myeloid leukemia.
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PROTAC Tubulin degrader-2
0 ImagesCat. No.: HY-181143PROTAC Tubulin degrader-2 is a cereblon (CRBN)-dependent α/β-tubulin PROTAC degrader with DC50 values of 1.73 μM and 1.38 μM. PROTAC Tubulin degrader-2 can inhibit cancer cells proliferation and migration. PROTAC Tubulin degrader-2 can induce G2/M arrest, apoptosis, ROS accumulation. PROTAC Tubulin degrader-2 can be used for the research of cancer, such as non-small-cell lung cancer.
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PROTAC SMARCA2/4 degrader-39
0 ImagesCat. No.: HY-178225CAS No.: 3099581-74-2
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Azo-PROTAC-4C-cis
0 ImagesCat. No.: HY-180985Azo-PROTAC-4C-cis is a BCR-ABL PROTAC degrader, and its degradation efficiency of BCR-ABL is much lower than that of its trans isomer Azo-PROTAC-4C-trans (HY-180983). Azo-PROTAC-4C-cis is the product of the conformational transformation of Azo-PROTAC-4C-trans under ultraviolet (UV) light irradiation. Azo-PROTAC-4C-cis can be converted into highly active Azo-PROTAC-4C-trans under visible light, thereby initiating protein degradation. Azo-PROTAC-4C-cis can be used for the study of myeloid leukemia.
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dAURK-4
0 ImagesdAURK-4 is a selective AURKA PROTAC degrader. dAURK-4 promotes ubiquitination and degradation of AURKA. dAURK-4 can be used in the research of glioblastoma and multiple myeloma.
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PROTAC HDAC8 Degrader-3
0 ImagesCat. No.: HY-181023PROTAC HDAC8 Degrader-3 (Compound BP1) is an efficient and selective HDAC8 PROTAC degrader with a DC50 of 20 nM. PROTAC HDAC8 Degrader-3 exhibits IC50 for HDAC8 and CRBN of 0.46 and 7.5 μM, respectively. PROTAC HDAC8 Degrader-3 exhibits potent anti-proliferative activity against MM.1S and HL-60 cells. PROTAC HDAC8 Degrader-3 can be used for research on multiple myeloma and acute myeloid leukemia.
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PROTAC BRD4 Degrader-46
0 ImagesCat. No.: HY-182801CAS No.: 2766179-68-2PROTAC BRD4 Degrader-46 is a heterobifunctional BRD4 PROTAC degrader. PROTAC BRD4 Degrader-46 binds to both BRD4 and CRBN, thereby triggering ubiquitination and proteasomal degradation of BRD4. PROTAC BRD4 Degrader-46 downregulates the levels of downstream BRD2, BRD3 and MYC. PROTAC BRD4 Degrader-46 can be used in the research of cancers such as multiple myeloma.
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PROTAC HPK1 Degrader-2
0 ImagesCat. No.: HY-162544CAS No.: 2893885-31-7PROTAC HPK1 Degrader-2 (compound 3) is a PROTAC degrader targeting hematopoietic progenitor kinase MAP4K1/HPK1, with a DC50 of 23 nM in human PBMCs. PROTAC HPK1 Degrader-2 is applicable for cancer research.
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BD-7148
0 ImagesCat. No.: HY-186267CAS No.: 3037514-35-2BD-7148 is a potent, highly selective BRD4 PROTAC degrader with a DC50 of 0.9 nM. BD-7148 binds to recombinant human BRD2-BD1, BRD2-BD2, BRD3-BD1, BRD3-BD2, BRD4-BD1 and BRD4-BD2 domain proteins, with Kd values ranging from 26 nM to 240 nM, and shows no binding preference for BRD4 domains over BRD2 or BRD3 domains. BD-7148 inhibits the growth of leukemia and breast cancer cells. BD-7148 can be used in the research of leukemia and breast cancer.
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SZU305
0 ImagesCat. No.: HY-181651SZU305 is a RAD51 PROTAC degrader, with DC50 values of 307.45 nM and 84.19 nM in SK-HEP-1 and Huh-7 cells, respectively. SZU305 inhibits DNA damage repair, induces cell cycle arrest and apoptosis. SZU305 moderately reduces the protein levels of IKZF1 and IKZF3 at high concentrations. SZU305 can be used in studies related to hepatocellular carcinoma.
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PROTAC EGFR degrader 16
0 ImagesCat. No.: HY-178242CAS No.: 2654821-07-3PROTAC EGFR degrader 16 is a selective EGFR PROTAC degrader with a DC50 value of < 50 nM. PROTAC EGFR degrader 16 can be used for the study of EGFR-driven cancerssuch as non-small cell lung cancer.
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BWA-6047
0 ImagesCat. No.: HY-176128BWA-6047 is an oral active PROTAC degrader targeting AR/AR-V7 and GSPT1 with DC50 values of 3.7, 3.0 and 1.2 nM in 22Rv1 cells. BWA-6047 suppresses the expression of AR downstream target genes and and transcriptional activity. BWA-6047 inhibits cancer cells proliferation, causes G1 phase cell cycle arrest and induces apoptosis. BWA-6047 increases cleaved-PARP-1 and cleaved-caspase-3 levels. BWA-6047 reduces growth of LNCaP xenograft tumors in mice models without obvious toxicity. BWA-6047 can be used for the research of prostate cancer.
