Rucaparib (AG014699) camsylate 是一种口服有效的PARP蛋白 (PARP-1, PARP-2 and PARP-3) 抑制剂，对 PARP-1 的Ki为 1.4 nM。Rucaparib camsylate 是六磷酸己糖脱氢酶 (H6PD) 抑制剂。Rucaparib camsylate 具有用于去势抵抗性前列腺癌 (CRPC) 研究的潜力。
| 生物活性 | Rucaparib (AG014699) camsylate is an orally active, potent inhibitor ofPARPproteins (PARP-1, PARP-2 and PARP-3) with aKiof 1.4 nM forPARP1. Rucaparib camsylate is a modesthexose-6-phosphate dehydrogenase (H6PD)inhibitor. Rucaparib camsylate has the potential for castration-resistant prostatecancer(CRPC) research[1][2][3][4]. |
| IC50& Target | PARP-1 1.4 nM (Ki) | PARP-2 | PARP-3 |
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体外研究
(In Vitro) | 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 LC50being 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].
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体内研究
(In Vivo) | 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].
| Animal Model: | Female CD-1 nude mice aged 10-12 weeks with Capan-1 cells[2] | | Dosage: | 10 mg/kg or 50, 150 mg/kg | | Administration: | 10 mg/kg for i.p. or 50, 150 mg/kg for p.o. | | Result: | Significantly inhibited the growth of the tumor. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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