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    DRUG CLASS:

    CDK2 inhibitor

    Related drugs:
    3d
    The evolving landscape of CDK2 inhibition in cancer: Therapeutic potential, clinical progress, and future directions. (PubMed, Crit Rev Oncol Hematol)
    This review provides a comprehensive and up-to-date synthesis of the multifaceted roles of CDK2 in cancer, examining the landscape of selective CDK2 inhibitors and next-generation degraders (PROTACs/Molecular Glues) currently in clinical pipelines. We critically analyze translational hurdles-including the quest for super-selectivity over CDK1, the validation of predictive biomarkers, and resistance mapping-to provide a strategic direction for the future of CDK2-based cancer therapeutics.
    Review • Journal
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    CCNE1 (Cyclin E1) • CDK1 (Cyclin-dependent kinase 1)
    5d
    Non-Genetic Mechanisms of Fractional Resistance to Abemaciclib in Dedifferentiated Liposarcoma. (PubMed, bioRxiv)
    Dedifferentiated liposarcoma is a rare mesenchymal malignancy driven by amplification of chromosome 12q13-15, which includes the oncogenes CDK4 and MDM2. These fractionally resistant cells were defined by selective enrichment of cyclin-dependent kinase 2 (CDK2), cyclin B1, and phosphorylated ribosomal protein S6 (pS6), and showed enhanced sensitivity to the CDK2 inhibitor, tagtociclib. Together, these findings reveal nongenetic cell cycle plasticity as a mechanism of escape from CDK4/6 inhibition in dedifferentiated liposarcoma and nominate CDK2 and the PI3K-mTOR pathway as candidate targets for combination therapy.
    Journal
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    MDM2 (E3 ubiquitin protein ligase) • CCNB1 (Cyclin B1)
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    Verzenio (abemaciclib) • tegtociclib (PF-07104091)
    9d
    BG-68501-101: A Study to Examine the Safety of Different Doses of BG-68501 Given to Participants With Advanced-Stage Tumors (clinicaltrials.gov)
    P1, N=103, Active, not recruiting, BeiGene | Recruiting --> Active, not recruiting | N=258 --> 103 | Trial completion date: Jul 2028 --> Aug 2026 | Trial primary completion date: Apr 2028 --> Aug 2026
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • First-in-human
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    HER-2 (Human epidermal growth factor receptor 2) • CDK2 (Cyclin-dependent kinase 2)
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    HER-2 negative
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    fulvestrant
    14d
    Lead Discovery via Scaffold Refinement: Structure-Guided Optimization of 1,2,4-Triazolo[1,5-a]Pyrimidines as Potent Dual EGFR/CDK-2 Inhibitors Targeting Colorectal Carcinoma. (PubMed, Drug Dev Res)
    Leads 12c, 12i, and 22 demonstrated potent kinase inhibition, with 22 yielding a CDK-2 IC₅₀ of 0.03 µM (seliciclib: 0.02 µM), and 12c delivering an EGFR IC₅₀ of 0.12 µM (erlotinib: 0.01 µM). Promising ADMET profiles and good drug likeness are evident in these leads. These data underscore the great potential of this scaffold for developing dual EGF/CDK-2 inhibitors aimed at resistance mechanisms in more aggressive cancers and can thus be pursued further in preclinical optimization.
    Journal
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    EGFR (Epidermal growth factor receptor) • BCL2 (B-cell CLL/lymphoma 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3)
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    erlotinib • seliciclib (CYC202)
    17d
    CGVV858A12101: Study of GVV858 as a single agent or in combination with endocrine therapy in patients with HR+/HER2- breast cancer and other advanced solid tumors (2025-521911-38-00)
    P1/2, N=55, Not yet recruiting, Novartis Pharma AG
    New P1/2 trial
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    fulvestrant • letrozole • goserelin acetate • leuprolide acetate for depot suspension
    25d
    CGVV858A12101: Study of GVV858 as a single agent or in combination with endocrine therapy in patients with HR+/HER2- breast cancer and other advanced solid tumors (2025-521911-38-00)
    P1/2, N=55, Not yet recruiting, Novartis Pharma AG | N=26 --> 55
    Enrollment change
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    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    fulvestrant • letrozole • goserelin acetate • leuprolide acetate for depot suspension
    1m
    A Study to Assess the Safety and Pharmacokinetics of INCB123667 When Administered Orally to Adult Participants With Moderate or Severe Hepatic Impairment (clinicaltrials.gov)
    P1, N=16, Not yet recruiting, Incyte Corporation
    New P1 trial
    1m
    A Study to Assess the Safety and Pharmacokinetics of INCB123667 When Administered Orally to Adult Participants With Severe Renal Impairment or End Stage Renal Disease (clinicaltrials.gov)
    P1, N=16, Not yet recruiting, Incyte Corporation
    New P1 trial
    1m
    MAESTRA 2: Study to Evaluate INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression (clinicaltrials.gov)
    P3, N=466, Recruiting, Incyte Corporation | N=286 --> 466
    Enrollment change • Trial initiation date • Platinum resistant
    |
    FOLR1 ( Folate receptor alpha )
    |
    gemcitabine • paclitaxel • pegylated liposomal doxorubicin • topotecan
    2ms
    MAESTRA 2: Study to Evaluate INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression (clinicaltrials.gov)
    P3, N=286, Recruiting, Incyte Corporation
    New P3 trial • Platinum resistant
    |
    FOLR1 ( Folate receptor alpha )
    |
    gemcitabine • paclitaxel • pegylated liposomal doxorubicin • topotecan
    2ms
    INCB123667-305: Phase 3 Study of INCB123667 Versus Investigator's Choice of Chemotherapy in Platinum Resistant Ovarian Cancer With Cyclin E1 Overexpression (2025-522748-42-00)
    P2/3, N=108, Not yet recruiting, Incyte Corp.
    New P2/3 trial • Platinum resistant
    |
    FOLR1 ( Folate receptor alpha )
    |
    FOLR1 expression
    |
    gemcitabine • paclitaxel • pegylated liposomal doxorubicin • topotecan
    2ms
    CGVV858A12101: Study of GVV858 as a single agent or in combination with endocrine therapy in patients with HR+/HER2- breast cancer and other advanced solid tumors (2025-521911-38-00)
    P1/2, N=26, Not yet recruiting, Novartis Pharma AG
    New P1/2 trial
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    fulvestrant • letrozole • goserelin acetate • leuprolide acetate for depot suspension