FRAX597 - PAK 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFRAX597Cat. No.: HY-15542ACAS No.: 1286739-19-2分式: CHClNOS分量: 558.1作靶点: PAK作通路: Cell Cycle/DNA Damage; Cytoskeleton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 : 14.29 mg/mL (25.60 mM; Nee

2、d ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 1.43 mg/mL (2.56 mM); Suspended solution; Need ultrasonic2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.43 mg/mL (2.56 mM); Suspended solution; Need ultrasonic3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecu

3、les 您边的抑制剂师www.MedChemESolubility: 1.43 mg/mL (2.56 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 FRAX597种有效的 I型 P21激活激酶 (PAK)抑制剂，作于 PAK1，2 和 3，IC50 分别为 8，13 和 19 nM。IC50 & Target PAK1 PAK2 PAK38 nM (IC50) 13 nM (IC50) 19 nM (IC50)体外研究 FRAX597 is determined to be a potent, ATP-competitive inhibitor of g

4、roup I PAKs (PAK 1-3), withbiochemical IC50 values as follows: PAK1 IC50=8 nM, PAK2 IC50=13 nM, PAK3 IC50=19 nM. The IC50toward PAK4, a member of group II PAKs is 10 M. At a concentration of 100 nM FRAX597 displays asignificant (80% inhibition) inhibitory capacity toward YES1 (87%), RET (82%), CSF1R

5、 (91%), TEK (87%),PAK1 (82%), and PAK2 (93%). When measured using the Kinase Glo Assay in the presence of 20 nMprotein and 1 M ATP, FRAX597 displayed an IC50 value of 48 nM against wild type PAK1, while IC50values against the V342F and V342Y PAK1 mutants are higher than 3 M and 2 M, respectively 1.体

6、内研究 Analysis of the flux reading for the animals in the two cohorts demonstrates a significantly slower tumorgrowth rate in FRAX597-treated mice compared with control mice. After 14 days of treatment the animals aresacrificed and the tumors excised and weighed. FRAX597-treated cohort shows significa

7、ntly lower averagetumor weight compared with the control cohort (0.55 g versus 1.87 g, p=0.0001) 1.PROTOCOLCell Assay 1 30,000 SC4 cells/well are plated in 12-well dishes in triplicate. Cell growth media with or without FRAX597 (1M) is replaced daily. At indicated time points, cells from individual

8、wells are trypsinized and counted using aCoulter counter. Statistical analysis is performed using a Students t test. For cell cycle analysis, cells areharvested, washed once with PBS and fixed in cold 70% ethanol. Fixed cells are resuspended in propidiumiodide (PI) buffer (50 g/mL PI, 250 mg/mL RNas

9、e A in PBS) and incubated overnight at 4C in the dark. Cellcycle distribution is evaluated using Coulter Epics XL flow cytometer. Data are analyzed using WinMDIsoftware 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Nf2-

10、/- SC4 Schwann cells are transduced by lentiviruses carrying pLuc-mCherry and sorted by FACS. 5104cells are transplanted into the sciatic nerve sheath of NOD/SCID mice (8 weeks of age) by intraneuralinjection. Tumor progression is monitored weekly by bioluminescence imaging (BLI) on an IVIS-200 syst

11、em.The representative images from bioluminescence imaging (BLI) of mice carrying orthotopic tumors treatedwith FRAX597 (100 mg/kg) or vehicle control at day 14 of treatment. NOD/SCID mice are injectedintraneurally with 5104 SC4/pLuc-mCherry cells and are enrolled into treatment after 10 days. Mice a

12、retreated daily for 14 days and imaged every 3 days to follow tumor development.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE户使本产品发表的科研献 Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Licciulli S, et al. FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2(NF2)-associated Schwannomas. J Biol Chem. 2013 Oct 4;288(40):29105-14.McePdfHei