瑞卡帕布樟脑磺酸盐作用机制 - Medchemexpress - MCE中国

1、Product Data SheetRucaparib CamsylateCat. No.: HY-102003CAS No.: 1859053-21-6分式: CHFNOS分量: 555.66作靶点: PARP作通路: Cell Cycle/DNA Damage; Epigenetics储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 83.33 mg/mL (149.97 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgCo

2、ncentration制备储备液1 mM 1.7997 mL 8.9983 mL 17.9966 mL5 mM 0.3599 mL 1.7997 mL 3.5993 mL10 mM 0.1800 mL 0.8998 mL 1.7997 mL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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制

3、澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.74 mM); Clear solution此案可获得 2.08 mg/mL (3.74 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL

4、 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (3.74 mM); Clear solution此案可获得 2.08 mg/mL (3.74 mM，饱和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄均匀。DMSO 储备液加到 900 L 20%

5、的 SBE-CD 理盐溶液中，混合3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (3.74 mM); Clear solution此案可获得 2.08 mg/mL (3.74 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Rucaparib CamsylatePARP 的抑制剂，对PARP1的 Ki 值为1.4 nM。也可结合PARP其他个

6、结构域。IC & Target PARP-11.4 nM (Ki)体外研究 Rucaparib is the most potent PARP inhibitor in enzyme assays (Ki, 1.4 nM), and a possible N-demethylationmetabolite of AG146441. The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-B, and is independent of SSB repair inhibiti

7、on. Rucaparib could target NF-B activated by DNA damage and overcometoxicity observed with classical NF-B inhibitors without compromising other vital inflammatory functions2.Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 M in permeabilised D283Med cells3.体内研究 Rucaparib and AG145

8、84 significantly (P 0.05) increases temozolomide toxicity. Rucaparib (1 mg/kg) significantlyincreases temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) results in a 50% increase in thetemozolomide-induced tumor growth delay1. Rucaparib is not toxic but significantly enhances temozolomide-

9、induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show thatRucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancytherapy3. Rucaparib significantly potentiates the cytotoxicity of topotecan an

10、d temozolomide in NB-1691, SH-SY-5Y,and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete andsustained tumor regression in NB1691 and SHSY5Y xenografts4.PROTOCOLKinase Assay 1 Inhibition of PARP activity in 5103 D283Med cells is measured using various

11、 concentrations of Rucaparib (0-1 M),compared with DMSO-only. Maximally stimulated PARP activity is measured in samples of permeabilised cells byimmunologica1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Medulloblastoma cell lines are se

12、eded in 96-well plates at a density of 1103, 3103 and 3103, respectively. At 24hours (D384Med) or 48 hours (D283Med and D425Med) after seeding, the cells are exposed to variousconcentrations of temozolomide in the presence or absence of 0.4 M Rucaparib. After 3 days (D425Med andD384Med) or 5 days (D

13、283Med) of culture, cell viability is evaluated by a XTT cell proliferation kit assay. Cell growth isexpressed as a percentage in relation to DMSO or 0.4 M Rucaparib-alone controls. The concentration oftemozolomide, alone or in combination with Rucaparib that inhibited growth by 50% (GI50) is calcul

14、ated. Thepotentiation factor 50 (PF50) is defined as the ratio of the GI50 of temozolomide in the presence of Rucaparib to theGI50 of temozolomide alone1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal A single dose of temozolomide is administrat

15、ed p.o. as a suspension in saline at 200 mg/kg either alone or inPage 2 of 3 www.MedChemEAdministration 1 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 sal

16、ts equivalent to 0.79 and 7.9mg/kg free AG14451 and AG14452 and 0.78 and 7.8 free AG14531 and AG14644). Control animals are treated witheither normal saline p.o. and i.p or normal saline p.o and PARP inhibitor 10 mg/kg i.p1.MCE has not independently confirmed the accuracy of these methods. They are

17、for reference only.户使本产品发表的科研献 Clin Cancer Res. 2017 Feb 15;23(4):1001-1011. Sens Actuators B Chem. 2018 Nov 10; 273:1047-1053. Sens Actuators B Chem. 2018, 259: 565-572. Talanta. 2018 Apr 1;180:127-132. J Mol Med (Berl). 2019 Aug;97(8):1183-1193.See more customer validations on HYPERLINK www.MedChe

18、mE www.MedChemEREFERENCES1. Thomas HD, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956.2. Hunter JE, et al. NF-B mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264.3. Daniel RA, et al. Central nervou