Rucaparib (AG014699) acetate is a highly effective oral inhibitor of PARP proteins, specifically targeting PARP-1, PARP-2, and PARP-3, with a Ki value of 1.4 nM for PARP1. Additionally, it exhibits inhibitory action on hexose-6-phosphate dehydrogenase (H6PD) to a moderate extent. Rucaparib acetate shows promise in the field of research for castration-resistant prostate cancer (CRPC). [1] [2] [3] [4]

Rucaparib (AG014699) acetate is a possible N-demethylation metabolite of AG14644 [1]. Rucaparib (0.1, 1, 10, 100 μM; 24 hours) acetate is cytotoxic and has the LC 50 being 5 μM in Capan-1 (BRCA2 mutant) cells and only 100 nM in MX-1 (BRCA1 mutant) cells [2]. The radio-sensitization by Rucaparib acetate is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib acetate can target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions [5]. Rucaparib acetate inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells [6].

Rucaparib (AG014699) acetate and AG14584 significantly increase Temozolomide toxicity. Rucaparib (1 mg/kg) acetate significantly increases Temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) acetate esults in a 50% increase in the temozolomide-induced tumor growth delay [1]. Rucaparib (10 mg/kg for i.p. or 50, 150 mg/kg for p.o.; daily for 5 days per week for 6 weeks) acetate significantly inhibits the growth of the tumor, and there is one complete tumor regression and two persistent partial regressions [2]. Rucaparib (150 mg/kg; p.o.; once per week for 6 weeks or three times per week for 6 weeks) acetate has greatest antitumor effect with three complete regressions [2]. Rucaparib acetate enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts [6].