Rucaparib (PF-01367338) is a PARP protein inhibitor (PARP-1 Ki=1.4 nM) and hexose hexose-6-phosphate dehydrogenase (H6PD) inhibitor with oral activity. Rucaparib exhibits antitumor activity, with activity against desmoplasia-resistant prostate cancer (CRPC).

PARP1:1.4 nM

方法: 胶质母细胞瘤细胞系 U251 和 U87MG 用 Rucaparib (0.2-100 µM) 处理 92 h，使用 MTT assay 检测细胞活力。
结果: Rucaparib 抑制 GBM U251 和 U87MG 癌症细胞的增殖，且呈剂量依赖性，IC50 值分别为 14.36 µM 和 15.00 µM。[1]
方法: 人神经母细胞瘤细胞 SK-N-BE(2c) 和人胶质母细胞瘤细胞 UVW/NAT 细胞用 Rucaparib (1-10 µM) 处理 1.5 h，再用 H2O2 (20 mM) 处理 20 min，通过 Immunofluorescence 检测 PARP-1 活性。
结果: Rucaparib 可诱导内源性 PARP-1 活性降低 50%。DNA 损伤剂 H2O2 处理后，PARP-1 活性显著增强，用 Rucaparib 处理后，H2O2 诱导的 PARP-1 活性增加降低到与未处理细胞相当的水平。[2]

方法: 为检测体内抗肿瘤活性，用 Rucaparib (4 mg/kg，腹腔注射) 和 BKM120 (15  mg/kg，口服给药) 给药携带 U87MG 异种移植物的 BALB/C nude 小鼠，每天一次，持续 16 天。
结果: 单独使用 BKM120 或 Rucaparib 治疗可显著抑制肿瘤体积和重量的生长。当联合使用时，与单独使用每种药物相比，肿瘤生长进一步受到抑制。在 16 天的治疗期结束时，联合治疗使肿瘤体积和肿瘤重量减少了 90% 以上。[1]

Inhibition of PARP activity in 5×103 D283Med cells is measured using various concentrations of Rucaparib (0-1 μM), compared with DMSO-only. Maximally stimulated PARP activity is measured in samples of permeabilised cells by immunologica.

Medulloblastoma cell lines are seeded in 96-well plates at a density of 1×103, 3×103 and 3×103, respectively. At 24 hours (D384Med) or 48 hours (D283Med and D425Med) after seeding, the cells are exposed to various concentrations of temozolomide in the presence or absence of 0.4 μM Rucaparib. After 3 days (D425Med and D384Med) or 5 days (D283Med) of culture, cell viability is evaluated by a XTT cell proliferation kit assay. Cell growth is expressed as a percentage in relation to DMSO or 0.4 μM Rucaparib-alone controls. The concentration of temozolomide, alone or in combination with Rucaparib that inhibited growth by 50% (GI50) is calculated. The potentiation factor 50 (PF50) is defined as the ratio of the GI50 of temozolomide in the presence of Rucaparib to the GI50 of temozolomide alone.

Rucaparib is formulated in saline.A single dose of temozolomide is administrated p.o. as a suspension in saline at 200 mg/kg either alone or in combination with a single i.p. administration of PARP inhibitor administered at 0.1 [Rucaparib and MS-AG14644 (equivalent to 0.078 mg/kg free AG14644 only)], 1.0, and 10 mg/kg (for the mesylate salts equivalent to 0.79 and 7.9 mg/kg free AG14451 and AG14452 and 0.78 and 7.8 free AG14531 and AG14644). Control animals are treated with either normal saline p.o. and i.p or normal saline p.o and PARP inhibitor 10 mg/kg i.p.