K-7174-DataSheet-MedChemExpress

Inhibitors, Agonists, Screening Data Sheet

BIOLOGICAL ACTIVITY: GW4869 is a noncompetitive neutral sphingomyelinase inhibitor with an IC50 of 1 μM.IC50 & Target: IC50: 1 μM (neutral sphingomyelinase)[1]In Vitro: GW4869 (10 μM) partially inhibits TNF–induced sphingomyelin (SM) hydrolysis, and 20 μM of the compound is protectedcompletely from the loss of SM. The addition of 10–20 μM GW4869 completely inhibits the initial accumulation of ceramide,whereas this effect is partially lost at later time points (24 h). The action of GW4869 occurs downstream of the drop in glutathione.GW4869 is able, in a dose–dependent manner, to significantly protect from cell death. These protective effects are accompanied bysignificant inhibition of cytochrome c release from mitochondria and caspase 9 activation, therefore localizing N–SMase activationupstream of mitochondrial dysfunction[1]. In Vivo: Pre–treatment with GW4869 significantly impairs release of both exosomes and pro–inflammatory cytokines (TNF–α, IL–1β,IL–6) in RAW264.7 macrophages. At 12 h after LPS treatment or CLP surgery, WT mice pretreated with GW4869 displays loweramounts of exosomes and pro–inflammatory cytokines in the serum than control PBS–injected mice. Accordingly, GW4869treatment diminishes the sepsis–induced cardiac inflammation, attenuates myocardial depression and prolongs survival[2]. PROTOCOL (Extracted from published papers and Only for reference) Kinase Assay:[1]B. cereu sphosphatidylcholine–PLC is incubated in the presence or absence of 10 μM GW4869 in a reaction mixturecontaining 100 mM Tris, pH 7.2, 25% glycerol, 20 mM p–nitrophenyl/phosphorylcholine, and production of p–nitrophenol isquantified spectrophotometrically at 410 nm. Protein phosphatase 2A from bovine kidney is incubated in the presence or absence ofGW4869 in buffer containing 50 mM Tris, pH 7.4, 1 mM dithiothreitol, 100 μM MnCl2, and 20% glycerol, and phosphatase activity ismeasured[1].Cell Assay: GW4869 is routinely stored at -80 °C as a 1.5 mM stock suspension in Me2SO. Right before use, the suspension issolubilized by the addition of 5% methane sulfonic acid (MSA) (2.5 μl of 5% MSA in sterile double–distilled H2O are added to 50μL of GW4869 stock suspension).[1]Cells are treated with GW4869 for 30 min and then TNF is added in 10 μL/well. At the indicatedtime points, 25 μL of MTT stock solution are added to each well and incubated at 37 °C in 5% CO2 for 3 h. The cell viability is usingthe MTT assay[1].Animal Administration: GW4869 is dissolved in DMSO (0.005%).[2]Mouse: The mice are randomly assigned to four groups: PBS,GW4869, PBS+LPS and GW4869+LPS (n=5 per group). GW4869 is intraperitoneally (i.p.) injected at one dose of 2.5μg/g. Mice inthe PBS+LPS group are pre–injected i.p. with PBS 1 h prior to an i.p. injection of LPS (25 μg/g). Mice in the group of GW4869+LPSare pre–injected i.p. with GW4869 (2.5μg/g) for 1 h, followed by an i.p. injection of LPS (25 μg/g, 100μl). Mice receive injections ofPBS to a comparable volume (100μl) as controls. The survival rate of the PBS+LPS and GW4869+LPS groups are monitored every 6h for a 36 h period[2].Product Name:GW4869Cat. No.:HY-19363CAS No.:6823-69-4Molecular Formula:C30H30Cl2N6O2Molecular Weight:577.50Target:OthersPathway:OthersSolubility:DMSO: 0.044 mg/mL (Need ultrasonic and warming)

Inhibitors, Agonists, Screening

Safety Data SheetRevision Date:Sep.-13-2017Print Date:Sep.-13-2017

1. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :Tofacitinib (citrate)

Catalog No. :HY-40354A

CAS No. :540737-29-91.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USA

Tel:609-228-6898

Fax:609-228-5909

E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-6898

2. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.

Inhibitors, Agonists, Screening Data SheetBIOLOGICAL ACTIVITY: KPT–9274 is an inhibitor of p21–activated kinase (PAK) extracted from patent WO 2015003166 A1; has an IC50 of less than 100 nM inMTT assay.IC50 & Target: IC50: less than 100 nM (PAK)PROTOCOL (Extracted from published papers and Only for reference) Cell assay [1]The cells were seeded at 5000–10000 cells in each well of 96–well plate in 100μL of fresh culture medium and were allowed to attachovernight. The stock solutions of the compounds were diluted in 100μL cell culture medium to obtain eight concentrations ofKPT–9274, ranging from 1 nM to 30 μM. After incubation for 64–72 hours, 20 μL of CellTiter 96 Aqueous One Solution Reagent wasadded to each well and the plate was returned to the incubator (37°C, 5%CO2) until an absolute OD of 1.5 was reached for the controlcells. All optical densities were measured at 490 nM using a Vmax Kinetic Microplate Reader.References: [1]. WO2015003166A1Product Name:KPT–9274Cat. No.:HY-12793CAS No.:1643913-93-2Molecular Formula:C35H29F3N4O3Molecular Weight:610.62Target:PAK; PAKPathway:Cytoskeleton; Cell Cycle/DNA DamageSolubility:DMSO: ≥ 32 mg/mL

Product Name:LY2608204

CAS No.: 1234703-40-2

Cat. No.:HY-13529Product Data Sheet

MWt:559.81

Formula:C28H37N3O3S3

Purity :>98%

Solubility:

25°C: DMSO 112 mg/mL Watery

Mechanisms:

Biological Activity:

Description: Pathways:Metabolism/Protease; Target:Glucokinaseg

<1 mg/mL Ethanol 35 mg/mL

Description:

C 50 value: 42nM (EC50).LY2608204 activates glucokinase (GK) with EC50 of 42 nM.

in vitro: LY2608204 activates glucokinase (GK) with EC50 of 42 nM at 10 mM glucose with a

concentration dependent manner at lower glucose concentrations. LY2608204 also stimulates

glucose metabolism in rat insulinoma INS1-E cells with EC50 of 579 nM.

in vivo: LY2608204 decreases plasma glucose in a dose-dependent manner at both fasted and

postprandial glucose levels. A maximal lowering of glucose AUC versus the untreated control group

is observed with the high dose (30 mg/kg) and represents a 42% decrease. Interpolation of the data