Rucaparib (AG-014699,PF-01367338) phosphate
(Synonyms: 瑞卡帕布磷酸盐; AG-014699 phosphate; PF-01367338 phosphate) 目录号 : GC15955
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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。
Cas No.:459868-92-9
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | LNCaP, C42B, PC3, DLD-1, MDA-MB-231, CAOV3, OVCAR-8 (prostate cancer and other cancer cell lines) |
Preparation Method | Cells were maintained in RPMI-1640 or DMEM supplemented with 10% fetal bovine serum (FBS) under standard conditions. Cells were treated with Rucaparib phosphate or DMSO for seven days. |
Reaction Conditions | 0.763nM-50μM; 7 days |
Applications | Rucaparib phosphate preferentially inhibited the growth of CDK12 knockout (KO) cells compared to isogenic wild-type cells. CDK12 KO cells were more sensitive to Rucaparib phosphate than control cells. |
| Animal experiment [2]: | |
Animal models | BALB/c mice with LP07 lung adenocarcinoma tumors |
Preparation Method | Mice were subcutaneously injected with LP07 lung adenocarcinoma cells to generate tumors. Tumor-bearing mice were randomized into two groups: non-treated (control) and treated with Rucaparib phosphate (150mg/kg; p.o.). Treatment started when tumors became measurable. |
Dosage form | 150mg/kg; p.o.; 20 days |
Applications | Rucaparib phosphate treatment significantly reduced tumor weight and tumor area compared to non-treated controls. Rucaparib phosphate decreased PARP activity and cell proliferation, while increasing DNA damage, TUNEL-positive nuclei, protein oxidation, and superoxide dismutase 2 content within the tumors. |
References: | |
| Cas No. | 459868-92-9 | SDF | |
| 别名 | 瑞卡帕布磷酸盐; AG-014699 phosphate; PF-01367338 phosphate | ||
| 化学名 | 8-fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate | ||
| Canonical SMILES | OP(O)(O)=O.FC1=CC2=C3C(CCNC2=O)=C(C4=CC=C(CNC)C=C4)NC3=C1 | ||
| 分子式 | C19H18FN3O.H3PO4 | 分子量 | 421.36 |
| 溶解度 | ≥ 21.1 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3733 mL | 11.8663 mL | 23.7327 mL |
| 5 mM | 474.7 μL | 2.3733 mL | 4.7465 mL |
| 10 mM | 237.3 μL | 1.1866 mL | 2.3733 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
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