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The discovery of BMS-737 as a potent, CYP17 lyase-selective inhibitor for the treatment of castration-resistant prostate cancer.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Nov2022, Vol. 75, pN.PAG-N.PAG. 1p. - Publication Year :
- 2022
-
Abstract
- [Display omitted] We report herein, the discovery of BMS-737 (compound 33) as a potent, non-steroidal, reversible small molecule inhibitor demonstrating 11-fold selectivity for CYP17 lyase over CYP17 hydroxylase, as well as a clean xenobiotic CYP profile for the treatment of castration-resistant prostate cancer (CRPC). Extensive SAR studies on the initial lead 1 at three different regions of the molecule resulted in the identification of BMS-737, which demonstrated a robust 83% lowering of testosterone without any significant perturbation of the mineralocorticoid and glucocorticoid levels in cynomologous monkeys in a 1-day PK/PD study. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CASTRATION-resistant prostate cancer
*SMALL molecules
*ABIRATERONE acetate
Subjects
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 75
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 159329639
- Full Text :
- https://doi.org/10.1016/j.bmcl.2022.128951