2. Signalwege
  3. PROTAC
  4. PROTACs
  5. Cereblon Isoform

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].

Cereblon Verwandte Produkte (225):

Art. -Nr. Produktname CAS. Nr. Reinheit Chemische Struktur
  • HY-111546
    BI-3663 2341740-84-7 99.84%
    BI-3663 is a highly selective PTK2/FAK PROTAC (DC50=30 nM), with Cereblon ligands to hijack E3 ligases for PTK2 degradation. BI-3663 inhibits PTK2 with an IC50 of 18 nM. BI-3663 is a PROTAC that composes of BI-4464 (HY-124625) linked to Pomalidomide (HY-10984) with a linker. Anti-cancer activity.
    BI-3663
  • HY-125835
    CP-10 2366268-80-4 98.41%
    CP-10 is a PROTAC connected by ligands for Cereblon and CDK, with highly selective, specific, and remarkable CDK6 degradation (DC50=2.1 nM). It inhibits proliferation of several haematopoietic cancer cells with impressive potency including multiple myeloma, and can still degrades mutated and overexpressed CDK6.
    CP-10
  • HY-123919
    TL13-112 2229037-19-6 98.01%
    TL13-112 is a potent and selective ALK-PROTAC degrader and inhibits ALK activity with an IC50 value of 0.14 nM. TL13-112 also prompts the degradation of additional kinases including Aurora A, FER, PTK2 and RPS6KA1 with IC50 values of 8550 nM, 42.4 nM, 25.4 nM, and 677 nM, respectively. TL13-112 is comprised of the conjugation of Ceritinib?(HY-15656) and the Cereblon ligand of Pomalidomide (HY-10984).
    TL13-112
  • HY-156591
    PROTAC MLKL Degrader-1 3032600-90-8 99.76%
    PROTAC MLKL Degrader-1 is a selective MLKL PROTAC degrader with a DC50 of 2.4 μM. PROTAC MLKL Degrader-1 blocks necroptosis without modulating the phosphorylation of RIPK1 or RIPK3, and exhibits a linear correlation between MLKL levels and necroptotic cell death.
    PROTAC MLKL Degrader-1
  • HY-153803
    GBD-9 2864408-92-2 99.91%
    GBD-9 is a degrader based on the E3 ubiquitin ligase CRBN that targets BTK and the G1 to S phase transition protein GSPT1. GBD-9 has both PROTAC and molecular glue properties by inducing ubiquitination and proteasomal degradation of target proteins. GBD-9 can efficiently degrade wild-type and mutant BTK (such as C481S mutation) and GSPT1. GBD-9 significantly inhibits tumor cell proliferation by inducing G1 phase arrest in cancer cells, downregulating anti-apoptotic proteins (BCL-2, MCL-1) and activating Caspase-3 to induce apoptosis. GBD-9 is mainly used in the research of hematological tumors such as diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML).
    GBD-9 is composed of E3 ubiquitin ligase ligand (pink part) 5-Aminothalidomide (HY-W023573), target protein ligand (blue part) Btk Inhibitor: IBT6A (HY-13036A), and PROTAC linker (black part) Nonanoic acid (HY-N7057).
    GBD-9
  • HY-122822
    GSK699 2260944-68-9 98.80%
    GSK699 is a KAT2A/B/PCAF/GCN5 PROTAC degrader. GSK699 induces proteasome-dependent degradation of KAT2A, KAT2B, PCAF and GCN5, regulates the histone acetyltransferase activity of the SAGA complex, and reduces the level of histone H3K9ac. GSK699 inhibits the growth of neuroblastoma, acute myeloid leukemia and small cell lung cancer cells. GSK699 reduces the production of inflammatory cytokines and chemokines, and impairs LPS-stimulated immune cell responses. GSK699 is applicable to research related to acute myeloid leukemia, small cell lung cancer, neuroblastoma and inflammatory diseases.
    GSK699
  • HY-111518
    JH-XI-10-02 2209085-22-1 99.73%
    JH-XI-10-02 is a PROTAC connected by ligands for Cereblon and CDK. JH-XI-10-02 is a highly potent and selective PROTAC CDK8 degrader, with an IC50 of 159 nM. JH-XI-10-02 causes proteasomal degradation, does not affect CDK8 mRNA levels. JH-XI-10-02 shows no effect on CDK19.
    JH-XI-10-02
  • HY-103634
    dFKBP-1 1799711-22-0 98.00%
    dFKBP-1 is a potent and PROTAC-based FKBP12 degrader. dFKBP-1 incorporates the ligand SLF (HY-114872) of FKBP12, the Thalidomide based Cereblon ligand and a linker.
    dFKBP-1
  • HY-169360
    SD-436 2497585-50-7 98.27%
    SD-436 is a highly selective and efficacious STAT3 PROTAC degrader (DC50: 0.5 μM), with IC50 of 19 nM (STAT3), 270 nM (STAT1), 360 nM (STAT4), >10 μM (STAT5) and >10 μM (STAT6). SD-436 promotes ubiquitination and degradation of STAT3, and induces tumor regression. SD-436 can be used for tumor research, such as leukemia and lymphoma (Pink: STAT3 ligand (HY-169361); Blue: E3 ligase ligand (HY-43722); Black: linker (HY-147052).
    SD-436
  • HY-145282
    MS170 2376136-61-5 98.68%
    MS170 is a potent and selective PROTAC AKT degrader. MS170 depletes cellular total AKT (T-AKT) with the DC50 value of 32 nM. MS170 binds to AKT1, AKT2, and AKT3 with Kds of 1.3 nM, 77 nM, and 6.5 nM, respectively.
    MS170
  • HY-162608
    PROTAC JAK1 degrader 1 3052553-20-2 99.97%
    PROTAC JAK1 degrader 1 is a JAK1 PROTAC degrader with a DC50 of 214 nM and an IC50 of 5.2 nM. PROTAC JAK1 degrader 1 inhibits the downstream JAK-STAT signaling pathway by degrading JAK1. PROTAC JAK1 degrader 1 exhibits antiproliferative activity in cells. PROTAC JAK1 degrader 1 can be used for research on leukemia.
    PROTAC JAK1 degrader 1
  • HY-158142
    PROTAC TYK2 degrader-1 2770470-20-5 99.55%
    PROTAC TYK2 degrader-1 is a TYK2 PROTAC degrader with a Dmax ≥ 60%. PROTAC TYK2 degrader-1 reduces the phosphorylation levels of IFNα-induced STAT1 (Tyr701) and STAT3 (Tyr705) in immune cells. PROTAC TYK2 degrader-1 can be used in research on cancer, inflammatory diseases, etc.
    PROTAC TYK2 degrader-1
  • HY-171770
    dAurAB5 3115765-45-9 99.03%
    dAurAB5 is a dual Aurora-A (DC50 = 8.8 nM) and Aurora-B (DC50 = 6.1 nM) PROTAC degrader. dAurAB5 induces degradation of Aurora-A and Aurora-B, reduces N-Myc levels, and decreases viability in IMR32 neuroblastoma cells. dAurAB5 downregulates the levels of AAK1, PTK2, GAK, and TTK. dAurAB5 can be used to study cancers such as neuroblastoma. (Pink: TTK ligand 2: HY-168542, Blue: Thalidomide-O-COOH: HY-103597, Black: 6-Aminocaproic acid: HY-B0236).
    dAurAB5
  • HY-171767
    SK2188 3038446-94-2 99.87%
    SK2188 is a highly efficient and selective PROTAC degrader targeting AURKA (DC50 = 3.9 nM). SK2188 induces DNA damage and cell apoptosis. SK2188 indirectly degrades MYCN, inhibits tumor cell proliferation, and provides insights into the study of MYCN-amplified neuroblastoma (Pink: AURKA ligand: MK-5108 (HY-13252); Blue: Thalidomide (HY-14658); Black: Linker: Amino-PEG4-alcohol (HY-W008005)).
    SK2188
  • HY-130122
    MG-277 2411085-89-5 98.68%
    MG-277, a molecular glue degrader, effectively induces degradation of a translation termination factor based on Cereblon E3 ligand, GSPT1, with a DC50 of 1.3 nM. MG-277 potently inhibits tumor cell growth in a p53-independent manner, with IC50s of 3.5 nM for RS4;11 cells and 3.4 nM for p53 mutant RS4;11/IRMI-2 cells, respectively. Anticancer activity.
    MG-277
  • HY-161536
    PROTAC EGFR degrader 9 2992670-33-2 98.35%
    PROTAC EGFR degrader 9 (Compound C6) is an orally active CRBN-based PROTAC EGFR degrader. PROTAC EGFR degrader 9 exhibits a DC50 of 10.2 nM and a Kd of 240.2 nM against EGFRL858R/T790M/C797S. PROTAC EGFR degrader 9 exhibits potent degradation activity against various EGFR mutants, while sparing the EGFRWT. (Blue: CRBN ligand (HY-A0003), Black: linker (HY-161613); Pink: EGFR inhibitor (HY-161537)).
    PROTAC EGFR degrader 9
  • HY-133137
    SJF620 2376187-16-3 98.98%
    SJF620 is a PROTAC connected by ligands for Cereblon and Btk with a DC50 of 7.9 nM. SJF620 contains a Lenalidomide analog for recruiting CRBN.
    SJF620
  • HY-139186
    PROTAC KRAS G12C degrader-1 2984236-79-3 99.15%
    PROTAC KRAS G12C degrader-1 is a Cereblon-based KRASG12C PROTAC degrader. PROTAC KRAS G12C degrader-1 induces CRBN/ KRASG12C dimerization and degrades GFP- KRASG12C in reporter cells.
    PROTAC KRAS G12C degrader-1
  • HY-128845
    PROTAC CRBN Degrader-1 2358775-70-7 98.77%
    PROTAC CRBN Degrader-1 (Compound 14a) is a VHL-CRBN heterodimerization PROTAC degrader that achieves a selective degradation of CRBN by binding two E3 ubiquitin ligases (VHL and CRBN) to each other. (Blue: VHL ligand (S,R,S)-AHPC (HY-125845); Pink: CRBN ligand Pomalidomide-C2-NH2 (HY-128846); Black: Linker (HY-128847))
    PROTAC CRBN Degrader-1
  • HY-130714
    TD-165 2305936-56-3 98.08%
    TD-165 is a PROTAC-based cereblon (CRBN) degrader. TD-165 comprises a?cereblon (CRBN)?ligand binding group, a linker and an?von Hippel-Landau (VHL)?binding group.
    TD-165