維利帕尼作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetVeliparibCat. No.: HY-10129CAS No.: 912444-00-9分式: CHNO分量: 244.29作靶點(diǎn): PARP; Autophagy作通路: Cell Cycle/DNA Damage; Epigenetics; Autophagy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 : 29 mg/mL (118.71 mM)* means soluble, but saturation unknown.

2、SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 4.0935 mL 20.4675 mL 40.9350 mL5 mM 0.8187 mL 4.0935 mL 8.1870 mL10 mM 0.4093 mL 2.0467 mL 4.0935 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

3、當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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: 2.5 mg/mL (10.23 mM); Clear solution此案可獲得 2.5 mg/mL (10.23 mM，飽和度未知) 的澄清溶液。以

4、 1 mL 作液為例，取 100 L 25.0 mg/mL 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: 2.5 mg/mL (10.23 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (10.23 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/

5、mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.23 mM); Clear solution此案可獲得 2.5 mg/mL (10.23 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 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Veliparib (ABT-888)種有效的 PARP 抑

6、制劑，抑制 PARP1 和 PARP2 的 Ki 分別為 5.2 和 2.9 nM。IC & Target PARP-2 PARP-1 Autophagy2.9 nM (Ki) 5.2 nM (Ki)體外研究 Veliparib (ABT-888) is also tested against SIRT2, an enzyme that also uses NAD+ for catalysis, and found to be inactive(5,000 nM). The receptor profile of Veliparib is determined in a panel of 74

7、 receptor-binding assays at aconcentration of 10 M. Veliparib displaces control-specific binding at 50% or greater at the human H1(61%), thehuman 5-HT1A (91%), and the human 5-HT7 (84%) sites only. The IC50s for these three receptors are 5.3, 1.5, and 1.2 M, respectively1. c-Met knockdown cells show

8、 4.2- (shMet-A; 95% CI=4-4.5) or 4.6-fold (shMet-B; 95% CI=4.4-4.8)growth inhibition when treated with 60 M Veliparib (ABT-888). When treated with 38 M Veliparib, c-Metknockdown cells show 2- (shMet-A; 95% CI=1.5-2.5) or 1.9-fold (shMet-B; 95% CI=1.3-2.5) growth inhibition2. InHaCaT cells, at 6 h po

9、st-treatment by Veliparib (ABT-888), cell viability is significantly increases under 1,000 M sulfurmustard (SM) exposure, whereas Veliparib does not protect cell viability under 100 M SM exposure. Moreover, theaddition of Veliparib no longer shows the protective effect at 24 h post SM exposure3.體內(nèi)研究

10、 Veliparib (ABT-888) is a potent inhibitor of PARP, has good oral bioavailability, can cross the blood-brain barrier insyngeneic and xenograft tumor models1. In MDA-MB-231 xenograft tumor models, combination treatment(AG014699/PF-02341066 and Veliparib (ABT-888)/Foretinib) substantially reduced tumo

11、r growth compared to eitherinhibitor alone2.PROTOCOLKinase Assay 2 PARP1 enzyme activity is measured by using a commercial assay kit with the exception that cell lysates containingwild-type PARP1 or PARP Y907 mutant are used in place of the PARP1 protein included with the kit. Total lysate (500ng) i

12、s added to each reaction. The dose course of PARP inhibitor Veliparib (ABT-888) is from 0.01 to 1,000 M. PARPenzyme activity of wild-type and mutants is determined after incubation with the substrate is measured using a platereader2.MCE has not independently confirmed the accuracy of these methods.

13、They are for reference only.Cell Assay 3 Cell viability is quantified using the Cell Counting Kit-8 (CCK-8). This assay is based on Dojindos highly water-solubletetrazolium salt. WST-8 is reduced by dehydrogenases in cells to give an orange, water-soluble formazan dye. Theamount of the formazan dye

14、generated by dehydrogenases in cells is directly proportional to the number of livingcells. Briefly, exponentially growing HaCaT cells are seeded in 96-well plates at a density of 10,000 cells/well. 6 h or 24h after exposure to sulfur mustard (SM) and the administration of Veliparib, the CCK-8 reage

15、nt is added3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemEAnimal Mice2Administration 2 MDA-MB-231 (0.5106), HCC1937 (2106) or MCF-7 (5106) cells are injected into the mammary fat pads of femalenude (Swiss Nu/Nu) mice of 6-8 we

16、eks of age. A1034 (0.5106) cells are injected into the mammary fat pads offemale FVB/NJ mice of 6-8 weeks of age. H1993 (0.5106) cells are injected subcutaneously into the right flank offemale nude (Swiss Nu/Nu) mice of 6-8 weeks of age. When the tumor volume reaches 50 mm3, PF-02341066 (5mg/kg) and

17、 Foretinib (5 mg/kg), AG014699 (5 mg/kg) and Veliparib (25 mg/kg), dissolved in aqueous 50 mM sodiumacetate, pH 4, are administered to mice five times per week as single agents or in combination for the number ofdays specified in the figure legend. Tumor is measured at the indicated time points, and

18、 tumor volume is calculatedby the formula: /6lengthwidth2. For MDA-MB-231 and A1034 xenograft mouse models, mice are imaged beforeand after treatment using the IVIS Imaging System to assess tumor growth. Mice are injected with 100 L of D-luciferin (15 mg/mL in PBS).MCE has not independently confirme

19、d the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cancer Discov. 2017 Sep;7(9):984-998. Clin Cancer Res. 2017 Feb 15;23(4):1001-1011. Mol Cancer Ther. 2019 Aug 14. pii: molcanther.0520.2019. J Mol Med (Berl). 2019 Aug;97(8):1183-1193. Neoplasia. 2019 Apr 24;21(6):533-544.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Donawho CK, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor th