China
Africa
Explore chapters and articles related to this topic
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Darolutamide acts as a selective competitive silent antagonist of the AR, blocking the effect of androgens such as testosterone and dihydrotestosterone (DHT). The major metabolite, ketodarolutamide, has similar anti-androgenic activity relative to darolutamide. However, although the parent molecule has a far shorter elimination half-life compared to enzalutamide (e.g., 1.6 hours versus 18.3 hours in mice), good clinical activity is observed with once-daily dosing. In addition to its actions as an AR antagonist, darolutamide acts as a silent antagonist of the progesterone receptor (PR) with approximately 1% of the potency of its AR antagonism.
Absorption, distribution, metabolism and excretion of darolutamide (a novel non-steroidal androgen receptor antagonist) in rats
Published in Xenobiotica, 2020
Päivi Taavitsainen, Hille Gieschen, Timo Korjamo, Marja Kähkönen, Chira Malmström, Olaf Prien, Michael Niehues, Steffen Sandmann, Wiebke Janssen, Mikko Koskinen
Darolutamide is a novel, selective AR antagonist developed for the treatment of non-metastatic CRPC; it was approved for this indication by the US Food and Drug Administration in July 2019 (Bayer HealthCare Pharmaceuticals Inc, 2019). It consists of a 1:1 mixture of two diastereoisomers, (S,R)-darolutamide and (S,S)-darolutamide; its major circulating metabolite in humans, keto-darolutamide (also known as M-1), is formed by oxidation of darolutamide’s secondary alcohol to ketone (Figure 1). Both diastereoisomers and keto-darolutamide are pharmacologically active, exhibiting similar pharmacologic activity in vitro (Moilanen et al., 2015).
Darolutamide in hormone-sensitive and castration-resistant prostate cancer
Published in Expert Review of Clinical Pharmacology, 2021
Valeria Emma Palmieri, Giandomenico Roviello, Alberto D’Angelo, Chiara Casadei, Ugo De Giorgi, Roberta Giorgione
Darolutamide (ODM-201) is a nonsteroidal androgen receptor antagonist. It is composed of a mixture (1:1) of two pharmacologically active diastereomers (ORM-16,497 and ORM-16,555), structurally different from other second-generation antiandrogens [22,26], keto-darolutamide (ORM-15,341) is the pharmacologically active metabolite (Figure 1).