Rucaparib phosphate

製品コードS1098 バッチS109814

印刷

化学情報

Chemical Structure Synonyms AG-014699 phosphate, PF-01367338 phosphate Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H18FN3O.H3PO4
分子量 421.36 CAS No. 459868-92-9
Solubility (25°C)* 体外 DMSO 84 mg/mL (199.35 mM)
Water 2 mg/mL (4.74 mM)
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Rucaparib phosphate is an inhibitor of PARP with Ki of 1.4 nM for PARP1 in a cell-free assay, also showing binding affinity to eight other PARP domains. Phase 3.
in vitro Rucaparib is a potent inhibitor of purified full-length human PARP-1 and shows higher inhibition of cellular PARP in LoVo and SW620 cells. Besides, Rucaparib binds detectably to eight other PARP domains, including PARP2, 3, 4, 10, 15, 16, TNKS1 and TNKS2. [1] [2] The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. [3] Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells. [4]
in vivo Rucaparib is not toxic but significantly enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy. [4] Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts. [5]
特徴 The first PARP inhibitor used in clinical trials combined with temozolomide.

プロトコル(参考用のみ)

キナーゼアッセイ Ki Determination
Inhibition of human full-length recombinant PARP-1 by [32P]NAD+ incorporation is measured. The [32P]ADP-ribose incorporated into acid insoluble material is quantified using a PhosphorImager. Ki is calculated by nonlinear regression analysis.
細胞アッセイ 細胞株 D425Med, D283Med and D384Med cells
濃度 0.4 μM
反応時間 3 or 5 days
実験の流れ 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.
動物実験 動物モデル CD-1 nude mice bearing established D283Med xenografts
投薬量 1 mg/kg
投与方法 One or four daily by i.p.

カスタマーフィードバック

Data from [Data independently produced by Eur J Cancer, 2014, 50(15), 2725-34]

Data from [Data independently produced by Eur J Cancer, 2014, 50(15), 2725-34]

Data from [Data independently produced by Oral Oncol, 2014, 50(9), 825-31]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro [ Int J Mol Sci, 2024, 25(2)886] PubMed: 38255960
BRCA2 Germline Mutations Identify Gastric Cancers Responsive to PARP Inhibitors [ Cancer Res, 2023, 83(10):1699-1710] PubMed: 37129948
The Sensitization of Triple-Negative Breast Cancers to Poly ADP Ribose Polymerase Inhibition Independent of BRCA1/2 Mutation Status by Chemically Modified microRNA-489 [ Cells, 2023, 13(1)49] PubMed: 38201253
Venadaparib Is a Novel and Selective PARP Inhibitor with Improved Physicochemical Properties, Efficacy, and Safety [ Mol Cancer Ther, 2023, 22(3):333-342] PubMed: 36808277
Establishment and Molecular Characterization of an In Vitro Model for PARPi-Resistant Ovarian Cancer [ Cancers (Basel), 2023, 15(15)3774] PubMed: 37568590
Slow Dissociation from the PARP1-HPF1 Complex Drives Inhibitor Potency [ Biochemistry, 2023, 62(16):2382-2390] PubMed: 37531469
A site-specific analysis of the ADP-Ribosylome unveils Homogeneous DNA Damage-Induced Serine ADP-Ribosylation across wild-type and BRCA-mutant Breast [ bioRxiv, 2023, 10.1101/2023.12.15.571635] PubMed: none
p53 controls choice between apoptotic and non-apoptotic death following DNA damage [ bioRxiv, 2023, 2023.01.17.524444] PubMed: 36712034
Intercellular transfer of activated STING triggered by RAB22A-mediated non-canonical autophagy promotes antitumor immunity [ Cell Res, 2022, 10.1038/s41422-022-00731-w] PubMed: 36280710
Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors [ Nat Cancer, 2022, 3(7):808-820] PubMed: 35637402

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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