Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELosmapimodCat.No.:HY-10402CASNo.:585543-15-3Synonyms:GSK-AHAB;GW856553X;SB856553分?式:C??H??FN?O?分?量:383.46作?靶點(diǎn):p38MAPK;Autophagy作?通路:MAPK/ERKPathway;Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)Ethanol:33.33mg/mL(86.92mM;Needultrasonic)DMSO:27.5mg/mL(71.72mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6078mL13.0392mL26.0783mL5mM0.5216mL2.6078mL5.2157mL10mM0.2608mL1.3039mL2.6078mL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備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請?jiān)?個?內(nèi)使?，-20°C儲存時，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.75mg/mL(7.17mM);Suspendedsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.75mg/mL(7.17mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.75mg/mL(7.17mM);Clearsolution4.請依序添加每種溶劑：10%EtOH>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(6.52mM);Suspendedsolution;Needultrasonic5.請依序添加每種溶劑：10%EtOH>>90%cornoilSolubility:≥2.5mg/mL(6.52mM);ClearsolutionBIOLOGICALACTIVITY?物活性Losmapimod(GSK-AHAB)?種有效的，具有?服活性的選擇性p38MAPK抑制劑，抑制p38α和p38β的pKi值分別為8.1和7.6[1]。IC50&TargetpKi:8.1(p38α),7.6(p38β)體內(nèi)研究Inthespontaneouslyhypertensivestroke-pronerat(SHR-SP),chronictreatmentwithGSK-AHABsignificantlyanddose-dependentlyimprovessurvival,endothelial-dependentand-independentvascularrelaxation,andindicesofrenalfunction,anditattenuatesdyslipidemia,hypertension,cardiacremodeling,plasmareninactivity(PRA),aldosterone,andinterleukin-1β(IL-1β)[1].PROTOCOLAnimalMaleSHR-SPs(n=70)arerandomlyassignedaccordingtobodyweightintofivegroups(n=14pergroup):Administration[1]normaldietcontrols(ND),highsalt-fatdietcontrols(SFD),SFD+GSK-AHAB(1.2mg/kg/day),andSFD+GSK-AHAB(12mg/kg/day)andSFD+MK966(18mg/kg/day).AlldrugsareadministeredinthedietbymixingwiththeSFD.Asubgroupofanimalsfromeachgroup(n=6pergroup)areanesthetizedandsurgicallyinstrumentedwithradiotelemetryunitsfortheconsciousmeasurementofmeanarterialbloodpressureandheartrate.Theseanimalsareallowedtorecoverforatleast7daysbeforethestartofthestudy.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?EBioMedicine.2018Feb;28:51-61.?CellSyst.2018Apr25;6(4):424-443.e7.?CellMolLifeSci.2022Aug5;79(8):467.?Aging(AlbanyNY).2021Aug10;13(15):19088-19107.?AmJPhysiolLungCellMolPhysiol.2012Nov15;303(10):L929-38.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].WilletteRN,etal.Differentialeffectsofp38mitogen-activatedproteinkinaseandcyclooxygenase2inhibitorsinamodelofcardiovasculardisease.JPharmacolExpTher.2009Sep;330(3):964-70.[2].ZhangXM,etal.Suppressionofmitochondrialfissioninexperimentalcerebralischemia:Thepotentialneuroprotectivetargetofp38MAPKinhibition.NeurochemInt.2015Nov;90:1-8.McePdfHeightCaution:Producthas