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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XYD270
0 ImagesCat. No.: HY-182082XYD270 is an orally active BRD9 PROTAC degrader. XYD270 inhibits the proliferation of cancer cells. XYD270 suppresses tumor growth in a mouse model of acute myeloid leukemia. XYD270 can be used in research related to synovial sarcoma and acute myeloid leukemia.
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DN1679
0 ImagesCat. No.: HY-181035DN1679 is a potent, selective and orally active CRBN-dependent CDK12/13 PROTAC dual degrader. DN1679 shows DC50 of 8.8/9.8 nM (MDA-MB-231), 5.1/6.4 nM (MDA-MB-157) and 17.2/15.8 nM (MDA-MB-468) for CDK12/13. DN1679 can downregulate DNA damage response gene mRNA levels, such as ATM, ATR, BRCA1 and RAD51. DN1679 demonstrates a potent synergistic anti-tumor effect companied with Olaparib (HY-10162). DN1679 can be used for research of triple-negative breast cance.
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LC-1-40
0 ImagesCat. No.: HY-158062Purity: 99.65%LC-1-40 is a selective NUDT1 PROTAC degrader with a DC50 of 0.97 nM. LC-1-40 recruits NUDT1 to the CRBN E3 ubiquitin ligase complex and mediates its degradation via a proteasome-dependent pathway. LC-1-40 induces increased nucleotide damage and Apoptosis in tumors. LC-1-40 can be used in studies related to Mycn-amplified neuroblastoma.
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DFCI-002-06
0 ImagesCat. No.: HY-181050CAS No.: 3092208-36-8DFCI-002-06 is an orally active dual-target HCK/BTK PROTAC degrader with DC₅₀ values for HCK and BTK of 1.3 and 4.5 nM respectively. DFCI-002-06 retains higher anti-tumor activity than the HCK/BTK dual-target inhibitor (HY-15805), inducing apoptosis in cancer cells. DFCI-002-06 can be used for the study of MYD88 mutant B-cell malignancies.
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KG-FP-003
0 ImagesCat. No.: HY-186117CAS No.: 3066008-42-9KG-FP-003 is a highly potent, selective, and durable TEAD PROTAC degrader (TEAD1 DC50 = 6 ± 4 nM, TEAD2 DC50 = 68 ± 15 nM, TEAD3 DC50 = 12 ± 5 nM, TEAD4 DC50 = 7 ± 5 nM). KG-FP-003 promotes ubiquitination and degradation of TEAD. KG-FP-003 exhibits anticancer activity against mesothelioma and ovarian cancer.
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CCT367766
0 ImagesCat. No.: HY-122653CAS No.: 2229856-58-8CCT367766 is a pirin PROTAC degrader. CCT367766 forms a ternary complex with cereblon and induces pirin depletion via the ubiquitin-proteasome pathway in a concentration- and time-dependent manner. CCT367766 can be used for ovarian cancer research.
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M4K3250
0 ImagesCat. No.: HY-183718M4K3250 is a selective ALK2 PROTAC degrader with a pDC50 of 7.9. M4K3250 induces the formation of a ternary complex between ALK2 and the E3 ubiquitin ligase CRBN, thereby causing ALK2 degradation and inhibiting ALK2 activity. M4K3250 exhibits cytotoxicity in glioblastoma cells. M4K3250 can be used in studies related to glioblastoma.
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FM-74-103
0 ImagesCat. No.: HY-184248FM-74-103 is a selective GSPT1 PROTAC degrader and broad-spectrum antiviral agent. FM-74-103 recruits GSPT1 to the Cereblon E3 ligase to form a ternary complex, thereby driving GSPT1 ubiquitination and proteasomal degradation. FM-74-103 inhibits the replication of IAV, SARS-CoV-2 and CMV (including Nucleozin (HY-50001)-resistant influenza A virus). FM-74-103 can be used in research related to influenza A virus infection, SARS-CoV-2 infection and cytomegalovirus infection.
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PROTAC mHTT Degrader-1
0 ImagesCat. No.: HY-181879CAS No.: 2919475-43-5PROTAC mHTT Degrader-1 is a blood-brain barrier-penetrant mutant huntingtin (mHTT) PROTAC degrader. PROTAC mHTT Degrader-1 specifically recognizes pathogenic mHTT aggregates and recruits Cereblon (CRBN), thereby inducing ubiquitination and proteasomal degradation of mHTT. PROTAC mHTT Degrader-1 alleviates mHTT-induced cytotoxicity and neuroinflammation. In the R6/2 Huntington's disease mouse model, PROTAC mHTT Degrader-1 reduces cerebral protein aggregation levels and improves body weight, motor coordination and survival rate of animals. PROTAC mHTT Degrader-1 can be used for research on PROTAC therapies for Huntington's disease and other neurodegenerative diseases.
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XYD224
0 ImagesCat. No.: HY-184210XYD224 is a selective BRD9 PROTAC degrader with a DC50 of 7.3 nM. XYD224 inhibits the proliferation of acute myeloid leukemia cells. XYD224 suppresses tumor growth in xenograft models. XYD224 is applicable for the research of acute myeloid leukemia (AML).
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SIAIS001
0 ImagesCat. No.: HY-171825CAS No.: 2570251-63-5SIAIS001 is a CRBN-dependent ALK PROTAC degrader with a DC50 of 3.9 nM. SIAIS001 induces ALK protein degradation via the ubiquitin-proteasome system. SIAIS001 induces G1/S phase cell cycle arrest and inhibits proliferation of cancer cells. SIAIS001 can be used for the research of anaplastic large-cell lymphomas.
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JQ1-S(GlcNAc)Cq
0 ImagesCat. No.: HY-178510JQ1-S (GlcNAc) Cq is a sugar-modified BRD4 PROTAC degrader with a DC50 of 2.1 μM. JQ1-S (GlcNAc) Cq inhibits the formation of the ternary complex between CRBN and BRD4 (BD1/BD2). JQ1-S (GlcNAc) Cq serves as a substrate for O-GlcNAcase, which cleaves its O-GlcNAc domain to restore binding ability with CRBN, thereby forming a BRD4-containing ternary complex and triggering ubiquitination and proteasomal degradation of BRD4. JQ1-S (GlcNAc) Cq is applicable for cancer research.
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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 FLT3/JAK2/BRD4 PROTAC degrader with DC50 values of 5.23, 0.68, and 1.17 nM, respectively. PROTAC FLT3/JAK2/BRD4 Degrader-1 induces cereblon- and proteasome-dependent degradation of FLT3, JAK2, and BRD4 via the ubiquitin-proteasome system. PROTAC FLT3/JAK2/BRD4 Degrader-1 is used in studies related to FLT3 inhibitor-resistant leukemia and acute myeloid leukemia.
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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 AR Degrader-10
0 ImagesCat. No.: HY-173372PROTAC AR Degrader-10 is a potent cereblon (CRBN)-recruited androgen receptor (AR) PROTAC degrader. PROTAC AR Degrader-10 exhibits high AR degradation activity and can be applied to research related to prostate cancer.
