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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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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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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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.
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SJ44236
0 ImagesCat. No.: HY-170900SJ44236 is a BET PROTAC degrader with activity against BRD2, BRD3 and BRD4 (DC50 = 127 pM). SJ44236 induces ubiquitination and proteasomal degradation by forming a ternary complex with BET proteins and CRBN-DDB1. SJ44236 downregulates c-Myc, upregulates p53 and reduces cancer cell viability. SJ44236 can be used for the research of leukemia and medulloblastoma.
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PROTAC AR Degrader-9
0 ImagesCat. No.: HY-170448PROTAC AR Degrader-9 is a topically applicable androgen receptor (AR) PROTAC degrader. PROTAC AR Degrader-9 recruits Cereblon (CRBN) E3 ubiquitin ligase to induce AR ubiquitination and proteasomal degradation in human dermal papilla cells (HDPCs) with a DC50 of 262.38 nM. PROTAC AR Degrader-9 possesses excellent skin retention, modulates androgenetic alopecia (AGA)-related downstream paracrine factors including TGF-β1 and β-catenin, promotes hair regeneration in mice. and exhibits favorable skin pharmacokinetics profiles with minimal systemic exposure. PROTAC AR Degrader-9 can be used for the study of androgenetic alopecia (AGA).
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IBA-12
0 ImagesCat. No.: HY-182799IBA-12 is a IKZF2 molecular glue/PROTAC degrader with a DC50 of 276.2 nM (Jurkat cells) and 461.8 nM (Mino cells), and an IC50 of 179.9 nM. IBA-12 binds to the canonical tryptophan triad pocket of CRBN to form a ternary complex with IKZF2. IBA-12 induces IKZF2 degradation mediated by the CRBN-dependent ubiquitin-proteasome system, with no effect on other CRBN substrates. IBA-12 induces the production of interleukin-2 (IL-2) through degrading IKZF2. IBA-12 is applicable to cancer immunology research.
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DeDPP4
0 ImagesCat. No.: HY-182336DeDPP4 is a DPP-4 PROTAC degrader. DeDPP4 induces sustained elevation of glucagon-like peptide-1 (GLP-1), enhances glucose tolerance, causes persistent reduction of blood glucose, and achieves long-term blood glucose regulation in animal models of type 2 diabetes. DeDPP4 mediates dose-dependent DPP-4 depletion in cancer cells, and also targets and degrades DPP-4 in the liver and adipose tissues of animal models with type 2 diabetes. DeDPP4 can be used for the research of type 2 diabetes and non-small cell lung cancer.
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PROTAC ERα Degrader-10
0 ImagesCat. No.: HY-170336CAS No.: 2421260-43-5PROTAC ERα Degrader-10 is an orally active estrogen receptor α (ERα) PROTAC degrader, with DC50 values of 0.37, 1.1, and 0.47 nM in MCF7, T47D, and CAMA-1 cells, respectively. PROTAC ERα Degrader-10 exhibits significant anti-tumor activity both in vitro and in vivo, and can be used for breast cancer research.
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PROTAC IRAK3 degrader-2
0 ImagesCat. No.: HY-181898CAS No.: 3072861-91-4
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PROTAC EGFR degrader 10
0 ImagesCat. No.: HY-161632CAS No.: 3034244-56-6PROTAC EGFR degrader 10 (Compound B56) is a PROTAC degrader for epidermal growth factor receptor (EGFR), with DC50 <100 nM. PROTAC EGFR degrader 10 binds CRBN-DDB1 with a Ki of 37 nM. PROTAC EGFR degrader 10 degrades EGFR, focal adhesion kinase (FAK), and RSK1, inhibits the proliferation of BaF3 wild type and EGFR mutants, with IC50 <150 nM.
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PROTAC SARS-CoV-2 RdRp Degrader-1
0 ImagesCat. No.: HY-179283PROTAC SARS-CoV-2 RdRp Degrader-1 (PROTAC 10) is a SARS-CoV-2 RdRp PROTAC degrader, with a DC50 of 1.97 μM (in infected cells). PROTAC SARS-CoV-2 RdRp Degrader-1 promotes the ubiquitination and degradation of SARS-CoV-2 RdRp. PROTAC SARS-CoV-2 RdRp Degrader-1 can be used in the research of SARS-CoV-2 infection.
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TD-802
0 ImagesCat. No.: HY-146397CAS No.: 2760703-21-5TD-802 is a CRBN-recruiting PROTAC androgen receptor (AR) degrader with liver microsomal stability and in vivo pharmacokinetic properties. TD-802 exhibits weak degrading activity against the AR-V7 splice variant, and its degradation process depends on the ubiquitin-proteasome system and Cullin-Ring ubiquitin ligase. TD-802 inhibits the proliferation of AR-dependent prostate cancer cells and the growth of AR-positive prostate cancer tumors in in vivo xenograft models.
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dCASP1-55
0 ImagesCat. No.: HY-181132dCASP1-55 is a cereblon-dependent caspase-1 (CASP1) PROTAC degrader. dCASP1-55 induces excessive NF-κB activation, apoptosis, and moderate S-phase arrest in leukemic cells. dCASP1-55 suppresses colony formation of leukemic cells. dCASP1-55 can be used for the research of cancer, such as myeloid malignancies and acute myeloid leukemia.
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PROTAC Sirt2 Degrader-2
0 ImagesCat. No.: HY-179388PROTAC Sirt2 Degrader-2 is a highly efficient and selective PROTAC degrader targeting SIRT2. PROTAC Sirt2 Degrader-2 demonstrates the most potent anti-proliferative activity both in vitro and in vivo. PROTAC Sirt2 Degrader-2 leads to a marked increase in H4K16Ac levels. PROTAC Sirt2 Degrader-2 significantly suppresses clonogenic formation and migration, induces cell cycle arrest, and promotes apoptosis. PROTAC Sirt2 Degrader-2 inhibits the AKT/mTOR signaling pathway by indirectly degrading SIRT2 and blocking downstream protein phosphorylation, thereby disrupting the signaling cascade and suppressing tumor development. PROTAC Sirt2 Degrader-2 can be used for the study of ovarian cancer.
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LWY713
0 ImagesCat. No.: HY-157213LWY713 is a FLT3 PROTAC degrader with a DC50 of 0.64 nM. LWY713 selectively induces FLT3 degradation in a cereblon- and proteasome-dependent manner. LWY713 induces G0/G1 cell cycle arrest and triggers apoptosis. LWY713 upregulates PARP and cleaved caspase 3, and inhibits the phosphorylation of FLT3, STAT5, AKT and Erk. LWY713 exhibits antitumor activity in xenograft mouse models. LWY713 can be used for the research of acute myeloid leukemia.
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MS910
0 ImagesCat. No.: HY-170982CAS No.: 2756323-28-9MS910 is an efficient and selective MEK1/2 PROTAC degrader. MS910 exhibits effective MEK1/2 degradation ability and anti proliferative activity in various cancer cells, such as HT-29 (MEK1 DC50 = 118 nM, MEK2 DC50 = 55 nM) and SK-MEL-28 (MEK1 DC50 = 94 nM, MEK2 DC50 = 38 nM) cells. MS910 is commonly used in cancer research. (Pink: MEK1/2 Ligand (HY-10254); Blue: CRBN Ligand (HY-W087383); Black: Linker (HY-W022240))
