Rucaparib camsylate  (Synonyms: AG014699 camsylate; PF-01367338 camsylate)

Rucaparib (AG014699) camsylate is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a K_i of 1.4 nM for PARP1. Rucaparib camsylate is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib camsylate has the potential for castration-resistant prostate cancer (CRPC) research^[1][2][3][4].

Rucaparib (AG014699) camsylate is a possible N-demethylation metabolite of AG14644^[1].
Rucaparib (0.1, 1, 10, 100 μM; 24 hours) camsylate is cytotoxic and has the LC₅₀ 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 camsylate is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib camsylate 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 camsylate inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Rucaparib (AG014699) camsylate and AG14584 significantly increase Temozolomide toxicity. Rucaparib (1 mg/kg) camsylate significantly increases Temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) camsylate results 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) camsylate 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) camsylate has greatest antitumor effect with three complete regressions^[2].
Rucaparib camsylate enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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• [1]. Thomas HD, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956.  [Content Brief]

  [2]. J Murray, et al. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Br J Cancer. 2014 Apr 15;110(8):1977-84.  [Content Brief]

  [3]. Matt Shirley, et al. Rucaparib: A Review in Ovarian Cancer. Target Oncol. 2019 Apr;14(2):237-246.  [Content Brief]

  [4]. Jianneng Li, et al. Hexose-6-phosphate dehydrogenase blockade reverses prostate cancer drug resistance in xenograft models by glucocorticoid inactivation. Sci Transl Med. 2021 May 26;13(595):eabe8226.  [Content Brief]

  [5]. Hunter JE, et al. NF-κB mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264.  [Content Brief]

  [6]. Daniel RA, et al. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res, 2009, 15(4), 1241-1249.  [Content Brief]