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    DRUG CLASS:

    GSPT1 degrader

    Related drugs:
    2ms
    GSPT1 degraders: research progress, development strategies and challenges. (PubMed, Bioorg Med Chem)
    Currently, several selective GSPT1-degraders have entered clinical trials. This review summarized the research progress of various GSPT1 degraders with an emphasis on their design, activity studies and development strategy, aiming to provide valuable insights for the further development of GSPT1 degraders.
    Review • Journal
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    CRBN (Cereblon) • GSPT1 (G1 To S Phase Transition 1)
    4ms
    Targeted degradation of GSPT1 and NEK7 by a molecular glue prodrug for treatment of HCC. (PubMed, Commun Chem)
    Targeted Protein Degradation (TPD) technology, in the form of CRBN-modulating molecular glues, offers numerous unprecedented therapeutic benefits as evidenced by the success of approved high-value immunomodulatory imide drugs (IMiDs) such as lenalidomide and pomalidomide. VAP-1, which is overexpressed in cirrhotic liver, was identified as the primary monoamine oxidase responsible for the conversion of ABS-752. ABS-752 is currently in clinical trials for the treatment of HCC.
    Journal
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    CRBN (Cereblon) • GSPT1 (G1 To S Phase Transition 1) • SALL4 (Spalt Like Transcription Factor 4)
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    lenalidomide • pomalidomide
    5ms
    Study of ORM-5029 in Subjects With HER2-Expressing Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=25, Terminated, Orum Therapeutics USA, Inc. | N=87 --> 25 | Trial completion date: Oct 2025 --> Jun 2025 | Active, not recruiting --> Terminated; Sponsor Decision
    Enrollment change • Trial completion date • Trial termination
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    HER-2 (Human epidermal growth factor receptor 2)
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    ORM-5029
    6ms
    Study of BMS-986497 (ORM-6151) as a Monotherapy, in Double and Triple Combination With Azacitidine and Venetoclax in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov)
    P1, N=105, Recruiting, Bristol-Myers Squibb | N=35 --> 105
    Enrollment change
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    Venclexta (venetoclax) • azacitidine
    6ms
    Study of CT-01 as Monotherapy and Combination Therapy in Subjects With Intermediate or Advanced Hepatocellular Carcinoma (clinicaltrials.gov)
    P1, N=141, Not yet recruiting, Captor Therapeutics S.A.
    New P1 trial
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    everolimus
    10ms
    Targeting MYC for the treatment of breast cancer: use of the novel MYC-GSPT1 degrader, GT19630. (PubMed, Invest New Drugs)
    We conclude that the novel molecular glue, GT19630, is a potent mediator of endpoints associated with cancer formation/progression. Its ability to degrade B7-H3 suggests that GT19630 may also promote host immunity against cancer. To progress GT19630 as a therapy for breast cancer, our finding should now be confirmed in an animal model system.
    Journal
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    CD276 (CD276 Molecule) • GSPT1 (G1 To S Phase Transition 1)
    10ms
    PROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia. (PubMed, Cancers (Basel))
    These findings suggest a new role of GSPT1 in regulating leukemic transcriptional networks and open a new therapeutic strategy to target leukemic fusion genes in pediatric AML patients.
    Journal
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    RUNX1 (RUNX Family Transcription Factor 1) • CRBN (Cereblon) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • CDK6 (Cyclin-dependent kinase 6) • ERG (ETS Transcription Factor ERG) • FUS (FUS RNA Binding Protein) • GSPT1 (G1 To S Phase Transition 1)
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    eragidomide (CC-90009)
    11ms
    Discovery of a Potent and Selective GSPT1 Molecular Glue Degrader for the Treatment of Castration-Resistant Prostate Cancer. (PubMed, J Med Chem)
    Importantly, 7d exhibits superior efficacy compared to 1 (CC-90009) in degrading GSPT1 in 22Rv1 cells with a DC50 value of 19 nM...Mechanistically, via degradation of GSPT1, 7d downregulates CRPC-related oncogenes in 22Rv1 cells, including AR, AR-V7, PSA, and c-Myc. Thus, our work provides a novel GSPT1 selective degrader with potent effectiveness in targeting Myc-driven CRPC.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor) • CRBN (Cereblon) • GSPT1 (G1 To S Phase Transition 1)
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    AR splice variant 7
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    eragidomide (CC-90009)
    11ms
    A Phase 1 Study of FD-001 in Recurrent /Refractory (R/R)AML/NHL/MM/MDS (clinicaltrials.gov)
    P1, N=72, Recruiting, Chengdu FenDi Pharmaceutical Co., Ltd. | Phase classification: P1/2 --> P1
    Phase classification
    12ms
    A Phase 1 Study of FD-001 in Recurrent /Refractory (R/R)AML/NHL/MM/MDS (clinicaltrials.gov)
    P1/2, N=72, Recruiting, Chengdu FenDi Pharmaceutical Co., Ltd.
    New P1/2 trial
    1year
    Study of ORM-5029 in Subjects with HER2-Expressing Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=87, Active, not recruiting, Orum Therapeutics USA, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    ORM-5029
    over1year
    Study of BMS-986497 (ORM-6151) in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov)
    P1, N=35, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting
    Enrollment open