Rucaparib (AG-014699,PF-01367338) phosphate is an orally bioavailable tricyclic indole poly (ADP-ribose) polymerase (PARP) inhibitor. Rucaparib phosphate blocks PARP-mediated DNA repair by selectively binding to and inhibiting the activity of PARP1 (Ki=1.4nM), PARP2, and PARP3, leading to accumulation of DNA strand breaks, genomic instability, and apoptosis. Rucaparib phosphate can be used in research related to BRCA mutation-associated ovarian cancer, fallopian tube cancer, primary peritoneal cancer, and metastatic castration-resistant prostate cancer (mCRPC)[1-4].
In vitro, Rucaparib phosphate (0.763nM-50μM) was used to treat CDK12 knockout (KO) prostate cancer cells (C42B, LNCaP) for 7 days. Rucaparib phosphate inhibited the growth of CDK12 KO cells[5]. Rucaparib phosphate (1.104-1.488μM) was combined with Trabectedin (0.352-2.64nM) to treat soft tissue sarcoma cell lines (IB115, IB111, IB136) for 72 hours. Rucaparib phosphate synergized with Trabectedin to inhibit cell proliferation, induce apoptosis, cause G2/M phase accumulation, and increase DNA damage[6].
In vivo, Rucaparib phosphate (150mg/kg) was orally administered to mice with lung adenocarcinoma (LP07) for 20 days. Rucaparib phosphate significantly reduced tumor burden, while decreasing PARP activity and cell proliferation, and increasing DNA damage, TUNEL-positive nuclei, protein oxidation, and SOD2 content[7]. Rucaparib phosphate (150mg/kg; five times per week) was orally administered to CD-1 nude mice bearing Capan-1 xenograft tumors for 6 weeks. Rucaparib phosphate significantly delayed tumor growth and induced tumor regression[8].
References:
[1] Fizazi K, Piulats JM, Reaume MN, et al. TRITON3 Investigators. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732.
[2] Thomas HD, Calabrese CR, Batey MA, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther. 2007 Mar;6(3):945-56.
[3] Syed YY. Rucaparib: First Global Approval. Drugs. 2017 Apr;77(5):585-592.
[4] Shirley M. Rucaparib: A Review in Ovarian Cancer. Target Oncol. 2019 Apr;14(2):237-246.
[5] Chou J, Robinson TM, Egusa EA, et al. Synthetic Lethal Targeting of CDK12-Deficient Prostate Cancer with PARP Inhibitors. Clin Cancer Res. 2024 Dec 2;30(23):5445-5458.
[6] Laroche A, Chaire V, Le Loarer F, et al. Activity of trabectedin and the PARP inhibitor rucaparib in soft-tissue sarcomas. J Hematol Oncol. 2017 Apr 11;10(1):84.
[7] Pérez-Peiró M, Valentí-Serra P, León-González B, et al. Attenuation of Tumor Burden in Response to Rucaparib in Lung Adenocarcinoma: The Contribution of Oxidative Stress, Apoptosis, and DNA Damage. Int J Mol Sci. 2023 Jan 30;24(3):2580.
[8] Murray J, Thomas H, Berry P, 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.
Rucaparib (AG-014699,PF-01367338) phosphate是一种口服生物可利用的三环吲哚类聚（ADP-核糖）聚合酶（PARP）抑制剂。Rucaparib phosphate通过选择性结合PARP1（Ki=1.4nM）、PARP2和PARP3并抑制其活性来阻断PARP介导的DNA修复，导致DNA链断裂积累、基因组不稳定和细胞凋亡。Rucaparib phosphate可用于BRCA突变相关的卵巢癌、输卵管癌、原发性腹膜癌以及转移性去势抵抗性前列腺癌(mCRPC)的相关研究[1-4]。
在体外，Rucaparib phosphate（0.763nM-50μM）处理CDK12敲除（KO）的前列腺癌细胞（C42B、LNCaP）7天。Rucaparib phosphate可抑制CDK12 KO细胞生长[5]。Rucaparib phosphate（1.104-1.488μM）与Trabectedin（0.352-2.64nM）联合处理软组织肉瘤细胞系（IB115、IB111、IB136）72小时。Rucaparib phosphate协同Trabectedin抑制细胞增殖，诱导细胞凋亡，导致G2/M期积累，同时增加DNA损伤[6]。
在体内，Rucaparib phosphate（150mg/kg）口服于肺腺癌（LP07）小鼠，持续20天。Rucaparib phosphate显著减少肿瘤负荷，降低PARP活性和细胞增殖，增加DNA损伤、TUNEL阳性细胞核、蛋白氧化和SOD2含量[7]。Rucaparib phosphate（150mg/kg；每周5次）和口服于携带Capan-1异种移植瘤的CD-1裸，持续6周。Rucaparib phosphate显著延迟了肿瘤生长并诱导肿瘤消退[8]。