FRAX486 _PAK 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFRAX486Cat. No.: HY-15542BCAS No.: 1232030-35-1分式: CHClFNO分量: 513.39作靶點(diǎn): PAK作通路: Cell Cycle/DNA Damage; Cytoskeleton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 : 21.2 mg/mL (41.29 mM; Nee

2、d ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.9478 mL 9.7392 mL 19.4784 mL5 mM 0.3896 mL 1.9478 mL 3.8957 mL10 mM 0.1948 mL 0.9739 mL 1.9478 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，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 FRAX486種 PAK抑制劑，對(duì) PAK1，PAK2 和 PAK3 的 IC50 值分別為 14，33 和 39

3、nM。IC50 & Target PAK1 PAK2 PAK314 nM (IC50) 33 nM (IC50) 39 nM (IC50)體外研究In vitro kinase assays using pure enzymes reveal IC50s for FRAX486 between 10-100 nM for PAK1-3, whilethe IC50 of 779 nM for PAK4 is just below the micromolar range. For FRAX486, an EC50 value of 500 nM1/3 Master of Small Molec

4、ules 您邊的抑制劑師www.MedChemEhas been reported from cells (5-50 fold higher than IC50). FRAX486 (30 M) inhibits endothelin-1 and -2induced contractions. In WPMY-1 cells, FRAX486 (24 h) induces concentration-dependent (1-10 M)degeneration of actin filaments. This is paralleled by attenuation of proliferat

5、ion rate, being observed from 1to 10 M FRAX486. Cytotoxicity of FRAX486 in WPMY-1 cells is time- and concentration-dependent.FRAX486 significantly reduces the relative proliferation rate in the remaining populations of WPMY-1 cells.While 68% of solvent-treated (24 h) cells shows proliferation, proli

6、feration rate after application of FRAX486(1-10 M, 24 h) ranges around 45%. FRAX486 (1-10 M, 24 h) causes concentration-dependentdegeneration of actin filaments. Actin filaments in solvent-treated control cells are arranged to bundles,forming long and thin protrusions, with elongations from adjacent

7、 cells overlapping each other. FRAX486 inconcentrations of 1 M causes partial loss of actin organization, including regressing degree of actinpolymerization and degeneration of protrusions. FRAX486 in concentrations of 5 or 10 M causes completebreakdown of filament organization, resulting in a round

8、ed cell shape without protrusions 1.體內(nèi)研究 FRAX486 displays the highest penetrance of bloodbrain barrier in DISC1-knockdown C57BL/6 mice. Dailyadministration of FRAX486, but not that of vehicle, between P35 and P60 blocks the exacerbated spine lossduring adolescence. In addition to the significant blo

9、ckade of spine elimination, a trend of enhanced spinegeneration is observed by treatment with FRAX486. FRAX486 treatment ameliorates a deficit in prepulseinhibition in adulthood 2.PROTOCOLCell Assay 1 WPMY-1 cells are plated with a density of 50,000/well on a 16-well chambered coverslip. After 24 h,

10、 cells aretreated with FRAX486 (1, 5, 10 M), IPA3 (1, 5, 10 M), or DMSO. After further 24 h, the medium is changedto a 10 mM 5-ethynyl-2-deoxyuridine (EdU) solution in FCS-free medium containing inhibitors or solvent. 20h later, cells were fixed with 3.7% formaldehyde. EdU incorporation is determine

11、d using the “EdU-Click 555”cell proliferation assay. In this assay, incorporation of EdU into DNA is assessed by detection with fluorescing5-carboxytetramethylrhodamine (5-TAMRA). Counterstaining of all nuclei is performed with DAPI. Cells areanalyzed by fluorescence microscopy (excitation: 546 nm;

12、emission: 479 nm) 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 The fasted male C57BL/6 mice are used. For FRAX486, i.v. dose is 3 mg/kg using a 1 mg/mL solution in20% (wt/vol) 2-hydroxypropyl-cyclodextrin in water, and

13、 per oral administration (o.s.) (PO) dose is 30mg/kg in a 3 mg/mL solution in water. For the in vivo experiment, FRAX486 is intraperitoneally administered10 g/BW (g) once daily from P35 to P60, which provides brain levels at 175 nM.MCE has not independently confirmed the accuracy of these methods. T

14、hey are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Am J Hum Genet. 2018 Oct 4;103(4):579-591.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Wang Y, et al. P21-Activated Kinase Inhibitors FRAX486 and IPA3: Inhibition of Prostate Stromal Cell Growth and Effects on SmoothMuscle Contraction in the Human Prostate. PLoS One. 2016 Apr 12;11(4):e0153312.2. Hayashi-Takagi A, et al. PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during lateadolescence. Proc Natl Acad Sci U S A. 201