Acalisib-GS-9820-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAcalisibCat. No.: HY-12644CAS No.: 870281-34-8Synonyms: GS-9820; CAL-120分式: CHFNO分量: 401.4作靶點(diǎn): PI3K作通路: PI3K/Akt/mTOR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 (72.25 mM)* mea

2、ns soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.4913 mL 12.4564 mL 24.9128 mL5 mM 0.4983 mL 2.4913 mL 4.9826 mL10 mM 0.2491 mL 1.2456 mL 2.4913 mL請根據(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，并請注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的?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，體內(nèi)實(shí)驗(yàn)的作液，建

3、議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.23 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.23 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.Med

4、ChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.23 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Acalisib種有效的選擇性 PI3K 抑制劑，IC50 為 12.7 nM。IC50 & Target p110 p110 p110 p11012.7 nM (IC50) 1389 nM (IC50) 3377 nM (IC50) 5441 nM (IC50)hVps34 DNA-PK12682 nM (IC50) 18749 nM (IC50)體外研究 Acalisib

5、(GS-9820) is more selective for PI3K (IC50=12.7 nM) relative to other PI3K class I enzymes (IC50:PI3K, 5,441 nM; PI3K, 3,377 nM; PI3K, 1,389 nM). Acalisib is also 103-fold more selective against PI3Kthan against related kinases, such as PI3KCII (IC5010 nM), hVPS34 (IC50=12.7 M), DNA-PK (IC50=18.7M),

6、 and mTOR (IC5010 nM). In fibroblasts, the PDGF receptor signals through PI3K and the GPCR forlysophosphatidic acid (LPA) signals through PI3K. Acalisib reduces PDGF-induced pAkt by only 50% at11,585 nM, and LPA-induced pAkt by 50% at 2,069 nM.體內(nèi)研究 To dissect the relative contribution of PI3K and PI

7、3K inhibition in the reduction of obesity, obesehyperphagic ob/ob mice are treated with a selective PI3K inhibitor, BYL-719, or with a selective PI3Kinhibitor, Acalisib (GS-9820). Remarkably, BYL-719 reduces body weight after 15 days of treatment to asimilar extent as CNIO-PI3Ki, whereas Acalisib ha

8、s no significant effect at the same doses as BYL-719. Itshould be noted that 10 mg/kg of Acalisib is sufficient to reduce the growth of multiple myeloma xenografts inmice 2.PROTOCOLKinase Assay 1 Biochemical in vitro lipid kinase assays are performed. A stock solution of Acalisib (GS-9820) is prepar

9、ed inDMSO at a concentration of 10 mM. Ten-point kinase inhibitory activities are measured over a concentrationrange (5 to 104 nM) with ATP at a concentration consistent with the Km of each of the enzymes 1.MCE has not independently confirmed the accuracy of these methods. They are for reference onl

10、y.Cell Assay 1 The effect of inhibitors on RAW264.7 cell survival is evaluated using the MTT assay. RAW264.7 cells areseeded in Falcon flat bottom 96-well plates at a density of 2.5-3104 cells/cm2 in 100 L of DMEM with 10%FBS and 1% antibiotic solution. After seeding, the cells are allowed to attach

11、 for 24 h then exposed to controlor Acalisib (GS-9820) (100 pM to 10 M) for 24 h. After incubation at 37C in 5% CO2, MTT substrate isadded at a final concentration of 0.5 mg/mL for 4 h. Following a 4-h incubation, 100 L of solubilizationsolution is added to each well to dissolve the formazan crystal

12、s and samples are analyzed after 24 h.Absorbance of the samples is assessed using a plate reader using a wavelength of 550 nm and a referencewavelength of 700 nm 1.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for referen

13、ce only.Animal Mice 2Administration 2 Ob/ob C57BL6J mice and Wild-type C57BL6J/Ola.Hsd mice are housed under specific pathogen free (SPF)conditions, at 22C, and with 12 hours dark/light cycles (light cycle from 8 am to 8 pm). All mice used aremales of 20 weeks of age. Mice are fed with standard chow

14、 diet (18% of fat-based caloric content). PI3Kinhibitors are administered daily by oral gavage during 15 or 16 days as follows, BYL-719 (5 and 10 mg/kg)and Acalisib (5 and 10 mg/kg), CNIO-PI3Ki (1 and 5 mg/kg), dissolved in PEG-300 and 10% N-methyl-2-pyrrolidone.MCE has not independently confirmed t

15、he accuracy of these methods. They are for reference only.REFERENCES1. Shugg RP, et al. Effects of isoform-selective phosphatidylinositol 3-kinase inhibitors on osteoclasts: actions on cytoskeletal organization,survival, and resorption. J Biol Chem. 2013 Dec 6;288(49):35346-57.2. Lopez-Guadamillas E, et al. PI3K inhibition reduces obesity in mice. Aging (Albany NY).