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    DRUG CLASS:

    CYP11A1 inhibitor

    Related drugs:
    23h
    Design, synthesis, and biological evaluation of cytochrome P450 CYP11A1 inhibitors. (PubMed, Bioorg Med Chem Lett)
    Based on the clinical candidate Opevesostat, two series of 23 new compounds were designed and synthesized using a 4H-pyran-4-one core to explore structure-activity relationships at the C2 and C6 positions.Compound II-4 exhibited potent inhibitory activity (95.2% at 100 nM; IC₅₀ = 26.7 nM), comparable to Opevesostat (IC₅₀ = 20.4 nM). Importantly, II-4 showed superior selectivity against CYP1A2, 2C9, and 2D6 (2- to 4-fold improvement), attributed to hydrophobic interactions between its C6 methyl group and Ile 84.These results highlight II-4 as a promising lead compound with optimized activity and selectivity, providing valuable insights for overcoming resistance in prostate cancer therapy.
    Journal
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    CYP1A2 (Cytochrome P450, family 1, subfamily A, polypeptide 2)
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    opevesostat (MK-5684)
    18d
    A Study to Evaluate Opevesostat (MK-5684) in Male Participants With Moderate Hepatic Impairment (MK-5684-009) (clinicaltrials.gov)
    P1, N=16, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed
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    prednisone • opevesostat (MK-5684)
    3ms
    OMAHA-004: A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004) (clinicaltrials.gov)
    P3, N=1314, Recruiting, Merck Sharp & Dohme LLC | Active, not recruiting --> Recruiting
    Enrollment open
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    Xtandi (enzalutamide) • abiraterone acetate • prednisone • dexamethasone • opevesostat (MK-5684) • Yonsa (abiraterone acetate)
    3ms
    Substudy 01A: Safety and Efficacy of Opevesostat (MK-5684)-Based Treatment Combinations or Opevesostat Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A) (clinicaltrials.gov)
    P1/2, N=220, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Mar 2028 --> Jan 2029 | Trial primary completion date: Mar 2028 --> Jan 2029
    Trial completion date • Trial primary completion date
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    Lynparza (olaparib) • docetaxel • prednisone • dexamethasone • cabazitaxel • opevesostat (MK-5684)
    3ms
    A Study to Evaluate the Effect of MK-5684 in Male Participants With Severe Renal Impairment (RI) and With End-stage Renal Disease (ESRD) (MK-5684-010) (clinicaltrials.gov)
    P1, N=24, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed
    Trial completion
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    prednisone • opevesostat (MK-5684)
    4ms
    OMAHA-004: A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004) (clinicaltrials.gov)
    P3, N=1314, Active, not recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Dec 2030 --> May 2028
    Trial primary completion date
    |
    Xtandi (enzalutamide) • abiraterone acetate • prednisone • dexamethasone • opevesostat (MK-5684) • Yonsa (abiraterone acetate)
    4ms
    A Study to Evaluate the Effect of MK-5684 in Male Participants With Severe Renal Impairment (RI) and With End-stage Renal Disease (ESRD) (MK-5684-010) (clinicaltrials.gov)
    P1, N=24, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed
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    prednisone • opevesostat (MK-5684)
    4ms
    OMAHA1: Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003) (clinicaltrials.gov)
    P3, N=1310, Recruiting, Merck Sharp & Dohme LLC | Active, not recruiting --> Recruiting
    Enrollment open
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    Xtandi (enzalutamide) • abiraterone acetate • prednisone • dexamethasone • opevesostat (MK-5684) • Yonsa (abiraterone acetate)
    5ms
    A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005) (clinicaltrials.gov)
    P1, N=6, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jan 2026 --> Apr 2026 | Trial primary completion date: Jan 2026 --> Apr 2026
    Trial completion date • Trial primary completion date
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    opevesostat (MK-5684)
    5ms
    A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of INV-9956 in Adult Patients With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=84, Recruiting, Shenzhen Ionova Life Sciences Co., Ltd. | Phase classification: P1 --> P1/2 | Trial completion date: Mar 2027 --> Jan 2028
    Phase classification • Trial completion date
    5ms
    OMAHA-004: A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004) (clinicaltrials.gov)
    P3, N=1500, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed
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    Xtandi (enzalutamide) • abiraterone acetate • prednisone • dexamethasone • opevesostat (MK-5684) • Yonsa (abiraterone acetate)
    6ms
    A Study of MK-5684 in People With Certain Solid Tumors (MK-5684-015/OMAHA-015) (clinicaltrials.gov)
    P2, N=250, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting | Trial completion date: Jul 2030 --> Nov 2027 | Trial primary completion date: Jul 2030 --> Nov 2027
    Enrollment open • Trial completion date • Trial primary completion date • Pan tumor
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    tamoxifen • fulvestrant • letrozole • exemestane • megestrol • opevesostat (MK-5684)