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    DRUG:

    opevesostat (MK-5684)

    i
    Other names: MK-5684, ODM-208, ODM 208, ODM208, MK 5684, MK5684
    Company:
    Merck (MSD), Orion Corp
    Drug class:
    CYP11A1 inhibitor
    Related drugs:
    1d
    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
    |
    CYP1A2 (Cytochrome P450, family 1, subfamily A, polypeptide 2)
    |
    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
    |
    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 • 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
    |
    Lynparza (olaparib) • docetaxel • prednisone • 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
    |
    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 • 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
    |
    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
    |
    Xtandi (enzalutamide) • abiraterone acetate • prednisone • 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
    |
    opevesostat (MK-5684)
    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
    |
    Xtandi (enzalutamide) • abiraterone acetate • prednisone • 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
    |
    tamoxifen • fulvestrant • letrozole • exemestane • megestrol • opevesostat (MK-5684)
    6ms
    CYPIDES: Safety and Pharmacokinetics of ODM-208 in Patients With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=204, Active, not recruiting, Orion Corporation, Orion Pharma | Trial completion date: Jun 2025 --> Jul 2026 | Trial primary completion date: Jun 2025 --> Jul 2026
    Trial completion date • Trial primary completion date
    |
    opevesostat (MK-5684) • midazolam hydrochloride