Definition

An orally bioavailable fixed dose combination agent containing the acetate ester prodrug of the steroidal compound abiraterone, an inhibitor of the cytochrome p450 (CYP) family member 17 alpha-hydroxylase/C17,20-lyase (CYP17; CYP17A1), and the tosylate monohydrate salt form of niraparib, an inhibitor of poly (ADP-ribose) polymerase (PARP) types 1 and 2 (PARP-1 and -2), with anti-androgen and antineoplastic activities. Upon administration of niraparib tosylate monohydrate and abiraterone acetate, abiraterone acetate is converted to its active form abiraterone, which, in turn, targets, binds to and inhibits the enzymatic activity of CYP17, thereby preventing the formation of steroid intermediates and androgens involved in androgen synthesis. This suppresses testosterone production by testes, adrenals and testosterone-dependent prostate tumor cells in order to decrease testosterone to castrate-range levels, which inhibits proliferation of testosterone-dependent cancer cells. In addition, niraparib binds to and inhibits the activity of PARP-1 and -2, thereby inhibiting PARP-1 and -2-mediated DNA repair, enhancing the accumulation of DNA strand breaks, and promoting genomic instability, which results in cancer cell apoptosis. PARP family proteins are often overexpressed in cancer cells and are activated by single-strand DNA (ssDNA) breaks to catalyze post-translational ADP-ribosylation of nuclear proteins, which promotes DNA repair and cancer cell survival.