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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JH-XII-03-02
0 ImagesJH-XII-03-02 is a potent and selective LRRK2 PROTAC degrader. JH-XII-03-02 promotes ubiquitination and degradation of LRRK2. JH-XII-03-02 can be used for the research of Parkinson's disease.
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SJ995973
0 ImagesSJ995973 is a BRD4 PROTAC degrader with DC50 values of 0.87 nM (12 h) and 0.16 nM (24 h), respectively. SJ995973 induces the formation of a ternary complex between purified BRD4 and CRBN-DDB1 proteins, with an IC50 of 17 nM against CRBN. SJ995973 inhibits the viability of human acute myeloid leukemia cells. SJ995973 can be used in studies related to acute myeloid leukemia and medulloblastoma.
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AH078
0 ImagesAH078 is a PROTAC-based CK1δ/ε degrader (DC50=0.55 μM, Dmax=70%) that lacks subtype selectivity between CK1δ and CK1ε. AH078 induces target protein degradation either by recruiting the CUL4-CRBN E3 ligase complex and proteasome, or via the VHL- and ubiquitin-dependent pathway. AH078 also exhibits selectivity for CK1α, and is widely applicable to research related to colon cancer, pancreatic cancer, breast cancer, ovarian cancer, chronic lymphocytic leukemia, acute myeloid leukemia, glioma, and metastatic breast adenocarcinoma.
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SB1-G-187
0 ImagesSB1-G-187 is a multi-target kinase PROTAC degrader with activity against various kinases including GCK, YES1, IRAK1 and LYN. SB1-G-187 induces degradation of target kinases via a p97-dependent pathway, and forms ternary complexes with CRBN and specific functional kinases. SB1-G-187 can be used in tumor-related research.
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dAURK-4 hydrochloride
0 ImagesCat. No.: HY-137344APurity: 99.57%dAURK-4 hydrochloride is a selective AURKA PROTAC degrader. dAURK-4 hydrochloride promotes ubiquitination and degradation of AURKA. dAURK-4 hydrochloride can be used in the research of glioblastoma and multiple myeloma.
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CG428
0 ImagesCG428 is a potent and selective CRBN-dependent tropomyosin receptor kinase (TRK) PROTAC degrader that has anti-tumor activity. CG428 reduces levels of the tropomyosin 3 TPM3-TRKA fusion protein in KM12 colorectal carcinoma cells (DC50 = 0.36 nM) and inhibits downstream PLCγ1 phosphorylation (IC50 = 0.33 nM). CG428 has a higher binding affinity for TRKA than TRKB and TRKC (Kd = 1 nM, 28 nM and 4.2 nM, respectively). CG428 can be used for the research of colorectal carcinoma.
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WZS0347
0 ImagesCat. No.: HY-179717Purity: 99.06%WZS0347 is a MITF PROTAC degrader. WZS0347 effectively reduces MITF protein levels in various melanoma cell lines. WZS0347 induces MITF degradation via the cereblon-dependent ubiquitin-proteasome pathway, downregulates the expression of downstream target genes of MITF, and inhibits the colony formation and migration abilities of cancer cells. WZS0347 can be used in melanoma-related research.
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SIAIS039
0 ImagesSIAIS039 is an orally active c-ros oncogene 1 (ROS1)-specific PROTAC with DC50s of 154.46 nM, 126.47 nM, 143.69 nM for HCC78 cells, Ba/F3 expressing the CD74-ROS1 fusion and Ba/F3 expressing the SDC4-ROS1 fusion, respectively. SIAIS039 suppresses cell proliferation, induces cell cycle arrest and apoptosis, and inhibits clonogenicity against ROS1-positive cells. SIAIS039 demonstrates anti-tumour effects against ROS1-driven tumor growth vivo. SIAIS039 is composed of the ALK inhibitor Brigatinib (HY-12857), a linker EM-12 (HY-138793), and a VHL ligand E3 ubiquitin ligase 1-Butyne (Red: Brigatinib; Blue: VHL ligand; Black: linker).
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PROTAC RIPK degrader-6
0 ImagesPROTAC RIPK degrader-6 (Example 1) is a RIPK2 PROTAC degrader that recruits cereblon. PROTAC RIPK degrader-6 recruits the CRBN E3 ubiquitin ligase complex and induces the degradation of RIPK2 kinase via the ubiquitin-proteasome pathway, thereby blocking NOD1/NOD2-mediated pro-inflammatory signaling pathways of NF-κB and MAPK. PROTAC RIPK degrader-6 can be used in research related to RIPK2-mediated autoinflammatory diseases and cancer.
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DZ-837
0 ImagesCat. No.: HY-161989CAS No.: 3105664-95-4DZ-837 is a BCL6 PROTAC degrader with a DC50 of 557.7 nM. DZ-837 induces BCL6 ubiquitination and degradation in a CRBN-dependent manner via the ubiquitin-proteasome system. DZ-837 activates CDKN1A and CDKN1B, the downstream genes of BCL6. DZ-837 upregulates p21 and p27 proteins. DZ-837 inhibits tumor growth in a diffuse large B-cell lymphoma xenograft mouse model. DZ-837 exerts synergistic antiproliferative effects when combined with Ibrutinib (HY-10997). DZ-837 can be used in studies related to diffuse large B-cell lymphoma.
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MD13
0 ImagesMD13 is a MIF PROTAC degrader with a DC50 of approximately 100 nM. MD13 induces ubiquitination and degradation of MIF by recruiting the Cereblon Cullin RING E3 ubiquitin ligase complex. MD13 inactivates the MAPK pathway and induces G2/M phase cell cycle arrest. MD13 exhibits antiproliferative effects in 3D tumor spheroid models. MD13 can be used in lung cancer-related research.
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CW-3308
0 ImagesCW-3308 is an orally active BRD9 PROTAC degrader with an DC50 of 92 nM. CW-3308 forms a ternary complex with BRD9 and cereblon to mediate BRD9 degradation. CW-3308 inhibits the viability of synovial sarcoma and rhabdoid tumor cells. CW-3308 reduces BRD9 protein levels in xenograft tumor tissues and suppresses tumor growth in xenograft models. CW-3308 can be used for the research of synovial sarcoma and rhabdoid tumors.
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PROTAC EGFR degrader 11
0 ImagesPROTAC EGFR degrader 11 (Compound B71) is a PROTAC degrader for epidermal growth factor receptor (EGFR), with DC50 <100 nM. PROTAC EGFR degrader 11 binds CRBN-DDB1 with a Ki of 36 nM. PROTAC EGFR degrader 11 degrades EGFR, focal adhesion kinase (FAK), and RSK1, inhibits the proliferation of BaF3 wild type and EGFR mutants, with IC50 <100 nM.
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RBN012811
0 ImagesRBN012811 is a highly selective PROTAC-based PARP14 degrader. RBN012811 forms a ternary complex with cereblon by binding to the NAD+ site of PARP14, and mediates the specific degradation of PARP14 via the ubiquitin-proteasome pathway (IC50=10 nM). RBN012811 effectively depletes endogenous PARP14 in various cell lines and primary human macrophages, thereby downregulating IL-10 production and IFN-β mRNA levels, increasing phosphorylated STAT1 levels to enhance inflammatory signaling, and inhibiting interferon-induced ADPr condensate formation. RBN012811 also modulates viral replication, exhibiting increased HSV1 replication while reducing VSV replication. RBN012811 has important application value in research related to cancer and viral infections.
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MS4322 (isomer)
0 ImagesSynonyms: YS43-22 (isomer)MS4322 (YS43-22) isomer is an isomer of MS4322. MS4322 is a specific PRMT5 PROTAC degrader. MS4322 reduces the PRMT5 protein level with a DC50 of 1.1 μM in MCF-7 cells. MS4322 inhibits the methyltransferase activity of PRMT5 with an IC50 of 18 nM. MS4322 promotes ubiquitination and degradation of PRMT5. MS4322 can be used for the research of breast cancer, lung cancer, and hepatocellular cancer.
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UBX-382
0 ImagesCat. No.: HY-160142CAS No.: 2884554-45-2UBX-382 is an orally active BTK PROTAC degrader with a DC50 of 4.56 nM. UBX-382 inhibits B-cell receptor signaling by targeting BTK. UBX-382 shows superior degradation activity for wild-type and mutant BTK proteins. UBX-382 inhibits tumor growth in murine xenograft models harboring wild-type or C481S mutant BTK-expressing TMD-8 cells. UBX-382 can be used for the study of B-cell-related blood cancers.
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Abd110
0 ImagesAbd110 is a selective ATR PROTAC degrader. Abd110 recruits Cereblon to induce the proteasomal degradation of ATR, and reduces the levels of phosphorylated ATR and downstream phosphorylated CHK1. Abd110 can be used for research on pancreatic cancer and cervical cancer.
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NU223612
0 ImagesNU223612 is a cereblon (CRBN)-recruiting IDO1 PROTAC degrader, with a DC50 value of 0.329-0.5438 μM against human IDO1, and it is capable of penetrating the blood-brain barrier. NU223612 directly binds to IDO1, mediates the degradation of both wild-type and catalytically inactive mutant IDO1 proteins, and does not degrade TDO2. NU223612 inhibits IDO1-mediated enzymatic activity. NU223612 directly binds to CRBN and promotes the formation of a cooperative ternary complex with IDO1. NU223612 induces ubiquitin-dependent proteasomal degradation of the IDO1 protein. NU223612 suppresses IDO1-mediated non-enzymatic phosphorylation of NF-κB p65 and the DNA-binding activity of downstream transcription factors. NU223612 can be used in studies of glioblastoma (malignant glioma).
