瑞卡帕布樟腦磺酸鹽作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetRucaparib CamsylateCat. No.: HY-102003CAS No.: 1859053-21-6分式: CHFNOS分量: 555.66作靶點(diǎn): PARP作通路: Cell Cycle/DNA Damage; Epigenetics儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 83.33 mg/mL (149.97 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgCo

2、ncentration制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制

3、澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.74 mM); Clear solution此案可獲得 2.08 mg/mL (3.74 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 20.8 mg/mL

4、 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (3.74 mM); Clear solution此案可獲得 2.08 mg/mL (3.74 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 20.8 mg/mL 的澄均勻。DMSO 儲(chǔ)備液加到 900 L 20%

5、的 SBE-CD 理鹽溶液中，混合3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (3.74 mM); Clear solution此案可獲得 2.08 mg/mL (3.74 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 20.8 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Rucaparib CamsylatePARP 的抑制劑，對(duì)PARP1的 Ki 值為1.4 nM。也可結(jié)合PARP其他個(gè)

6、結(jié)構(gòu)域。IC & Target PARP-11.4 nM (Ki)體外研究 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.體內(nèi)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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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