ORM-15341
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| Clinical data | |
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| Synonyms | BAY-1896953 |
| Drug class | Nonsteroidal antiandrogen |
| Pharmacokinetic data | |
| Elimination half-life | 10.0 hours[1] |
| Identifiers | |
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| CAS Number | |
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| Chemical and physical data | |
| Formula | C19H17ClN6O2 |
| Molar mass | 396.835 g/mol |
| 3D model (JSmol) | |
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ORM-15341, also known as BAY-1896953, is a nonsteroidal antiandrogen (NSAA) and the major active metabolite of darolutamide (ODM-201, BAY-1841788), an NSAA which is under development as a hormonal antineoplastic agent for the treatment of metastatic prostate cancer.[2][3][4][5] Similarly to its parent compound, ORM-15341 acts as a highly selective, high-affinity, competitive silent antagonist of the androgen receptor (AR).[2][3][4][5] Both agents show much higher affinity and more potent inhibition of the AR relative to the other NSAAs enzalutamide and apalutamide, although they also possess much shorter and comparatively less favorable terminal half-lives.[2][3][4][5] They have also been found not to activate certain mutant AR variants that enzalutamide and apalutamide do activate.[2][3][4][5] Both darolutamide and ORM-15341 show limited central nervous system distribution, indicating peripheral selectivity, and little or no inhibition or induction of cytochrome P450 enzymes such as CYP3A4, unlike enzalutamide and apalutamide.[2][3][4][5]
References
- ↑ Fizazi K, Massard C, Bono P, Jones R, Kataja V, James N, Garcia JA, Protheroe A, Tammela TL, Elliott T, Mattila L, Aspegren J, Vuorela A, Langmuir P, Mustonen M (2014). "Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial". Lancet Oncol. 15 (9): 975–85. doi:10.1016/S1470-2045(14)70240-2. PMID 24974051.
- 1 2 3 4 5 Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, Nykänen PS, Törmäkangas OP, Palvimo JJ, Kallio PJ (2015). "Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies". Sci Rep. 5: 12007. doi:10.1038/srep12007. PMC 4490394. PMID 26137992.
- 1 2 3 4 5 Fizazi K, Albiges L, Loriot Y, Massard C (2015). "ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer". Expert Rev Anticancer Ther. 15 (9): 1007–17. doi:10.1586/14737140.2015.1081566. PMC 4673554. PMID 26313416.
- 1 2 3 4 5 Shore ND (2017). "Darolutamide (ODM-201) for the treatment of prostate cancer". Expert Opin Pharmacother. 18 (9): 945–952. doi:10.1080/14656566.2017.1329820. PMID 28490267.
- 1 2 3 4 5 Comprehensive Medicinal Chemistry III. Elsevier Science. 3 June 2017. pp. 4–. ISBN 978-0-12-803201-5.
External links