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 (280)
Related Products (280)
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ZJK-807
0 ImagesCat. No.: HY-178497ZJK-807 is a highly efficient and selective KRASG12D PROTAC degrader (DC50 = 79.5 nM in AsPC-1 cells). ZJK-807 promotes KRASG12D ubiquitination and degradation. ZJK-807 suppresses RAS/MAPK signaling and uniquely modulates TNF signaling and eukaryotic ribosome biogenesis. ZJK-807 can be used for the study of KRAS-driven pancreatic cancer.
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PROTAC FLT3/JAK2/BRD4 Degrader-1
0 ImagesCat. No.: HY-175610CAS No.: 3067695-20-6PROTAC FLT3/JAK2/BRD4 Degrader-1 is a PROTAC degrader that target FLT3, JAK2, and BRD4 with DC50 values of 5.23, 0.678, and 1.17 nM, respectively. PROTAC FLT3/JAK2/BRD4 Degrader-1 exhibits potent antiproliferative activity against MV4;11 cells (IC50 = 0.79 nM) and FLT3 mutant-transformed Ba/F3 cells. PROTAC FLT3/JAK2/BRD4 Degrader-1 induces apoptosis in MV4;11 cells. PROTAC FLT3/JAK2/BRD4 Degrader-1 demonstrates significant anti-tumor efficacy in the MV4;11 xenograft model established in NOD SCID mice. PROTAC FLT3/JAK2/BRD4 Degrader-1 can be used for the study of acute myeloid leukemia (AML).
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PROTAC BRD4 Degrader-26
0 ImagesCat. No.: HY-161650CAS No.: 3050769-37-1PROTAC BRD4 Degrader-26 is a light-regulated BRD4 PROTAC degrader. PROTAC BRD4 Degrader-26 induces targeted degradation of BRD4 via the ubiquitin-proteasome system. PROTAC BRD4 Degrader-26 is a degrader that can be inactivated in response to ultraviolet light. PROTAC BRD4 Degrader-26 can be used in breast cancer-related research.
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PROTAC CB1R Degrader-1
0 ImagesCat. No.: HY-178176PROTAC CB1R Degrader-1 is a potent and selective CB1R PROTAC degrader that exploits the ubiquitin-proteasome system (UPS) achieving a DC50 of 3.37 μM in MCF-7 cells and showing no impact on CB2R. PROTAC CB1R Degrader-1 reduces CB1R-associated downstream signaling (p-AKT, p-ERK, BCL2, and MCM5), thereby inhibiting breast cancer cell proliferation and inducing apoptosis. PROTAC CB1R Degrader-1 can be used for breast cancer research.
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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 selective FAK PROTAC degrader (DC50 = 1.08 nM). PROTAC FAK degrader 3 induces FAK degradation dependent on the ubiquitin-proteasome system and its binding to FAK and CRBN. PROTAC FAK degrader 3 upregulates MHC-I gene transcription and tumor cell surface expression by inhibiting the non-catalytic activity of FAK, leading to increased antigen presentation and activation of cytotoxic CD8 T cells. PROTAC FAK degrader 3 enhances in vivo anti-tumor activity by promoting MHC-I expression and enhancing T cell activation. PROTAC FAK degrader 3 can be used in cancer research targeting FAK degradation in ovarian cancer, hepatocellular carcinoma, and other cancers.
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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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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.
