Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrariesML380Cat.No.:HY-12439CASNo.:1627138-52-6分?式:C??H??F?N?O?S分?量:494.53作?靶點:mAChR作?通路:GPCR/GProtein;NeuronalSignaling儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:100mg/mL(202.21mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0221mL10.1106mL20.2212mL5mM0.4044mL2.0221mL4.0442mL10mM0.2022mL1.0111mL2.0221mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存?式和期限。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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：為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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沉淀、析出現象，可以通過加熱和/或超聲的?式助溶1.請依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:2.5mg/mL(5.06mM);Suspendedsolution;Needultrasonic此?案可獲得2.5mg/mL(5.06mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述2.體系中加?50μLTween-80，混合均勻；然后繼續加?450μL?理鹽?定容?1mL。請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.5mg/mL(5.06mM);Clearsolution1/2此?案可獲得≥2.5mg/mL(5.06mM，飽和度未知)的澄溶液，此?案不適?于實驗周期在半個?以上的實驗。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性ML380?種有效的，亞型選擇性和可透過?腦屏障的M5mAChR正變構調節劑(PAM)，對?和??M5的EC50值分別為190和610nM。ML380對M1和M3mAChR亞型具有中等選擇性。ML380可以增加Ach對M5mAChR的親和?。IC50&TargetIC50:190nM(hM5),610nM(rM5)[1]體外研究ML380(0.01nM-100μM)robustlystimulatesinositolphosphate(IP)accumulationandCa2+mobilizationinCHO-hM5cells,withpEC50sof5.33and5.71,respectively[2].ML380(0.01-30μM)increasestheACh-stimulatedIPaccumulationandCa2+mobilizationinCHO-hM5cells[2].體內研究ML380(1mg/kg;i.v.)displayshighclearance(66mL/min/kg),amoderatevolumeofdistribution(1.6L/kg),andashorthalf-life(t1/2,22min)inrats[1].REFERENCES[1].GentryPR,et,al.Developmentofahighlypotent,novelM5positiveallostericmodulator(PAM)demonstratingCNSexposure:1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide(ML380).JMedChem.2014Sep25;57(18):7804-10.[2].BerizziAE,et,al.MolecularMechanismsofActionofM5MuscarinicAcetylcholineReceptorAllostericModulators.MolPharmacol.2016Oct;90(4):427-36.[3].BerizziAE,et,al.Structure-ActivityRelationshipsofPan-Gαq/11CoupledMuscarinicAcetylcholineReceptorPositiveAllostericModulators.ACSChemNeurosci.2018Jul18;9(7):1818-1828.McePdfHeightMedChemExpress(MCE)只為有