Chemistry:Ketodarolutamide
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| Other names | ORM-15341; BAY-1896953 |
| Drug class | Nonsteroidal antiandrogen |
| Pharmacokinetic data | |
| Elimination half-life | 10.0 hours[1] |
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| Chemical and physical data | |
| Formula | C19H17ClN6O2 |
| Molar mass | 396.84 g·mol−1 |
| 3D model (JSmol) | |
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Ketodarolutamide (developmental code names ORM-15341, BAY-1896953) is a nonsteroidal antiandrogen (NSAA) and the major active metabolite of darolutamide (ODM-201, BAY-1841788), an NSAA which is used in the treatment of prostate cancer in men.[2][3][4][5] Similarly to its parent compound, ketodarolutamide 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 elimination 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 ketodarolutamide 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
- ↑ "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. 2014. doi:10.1016/S1470-2045(14)70240-2. PMID 24974051. http://orca.cf.ac.uk/120395/1/JONES%2C%20Robert%20-%20Activity%20and%20safety%20of%20ODM-201%20in%20patients%20with%20progressive.pdf.
- ↑ 2.0 2.1 2.2 2.3 2.4 "Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies". Sci Rep 5: 12007. 2015. doi:10.1038/srep12007. PMID 26137992. Bibcode: 2015NatSR...512007M.
- ↑ 3.0 3.1 3.2 3.3 3.4 "ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer". Expert Rev Anticancer Ther 15 (9): 1007–17. 2015. doi:10.1586/14737140.2015.1081566. PMID 26313416.
- ↑ 4.0 4.1 4.2 4.3 4.4 "Darolutamide (ODM-201) for the treatment of prostate cancer". Expert Opin Pharmacother 18 (9): 945–952. 2017. doi:10.1080/14656566.2017.1329820. PMID 28490267.
- ↑ 5.0 5.1 5.2 5.3 5.4 Comprehensive Medicinal Chemistry III. Elsevier Science. 3 June 2017. pp. 4–. ISBN 978-0-12-803201-5. https://books.google.com/books?id=iZHUDQAAQBAJ&pg=RA4-PA142.
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