Camicinal-GSK962040-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECamicinalCat.No.:HY-10922CASNo.:923565-21-3Synonyms:GSK962040分?式:C??H??FN?O分?量:424.55作?靶點:MotilinReceptor作?通路:GPCR/GProtein儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(235.54mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3554mL11.7772mL23.5544mL5mM0.4711mL2.3554mL4.7109mL10mM0.2355mL1.1777mL2.3554mL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，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?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：(為保證實驗結(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)實驗的?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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.89mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.89mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.89mM);ClearsolutionBIOLOGICALACTIVITY?物活性Camicinal(GSK962040)胃動素受體激動劑，pEC50為7.9。IC50&TargetpEC50:7.9(MotilinReceptor)[1].體外研究Camicinal(GSK962040)hadnosignificantactivityatarangeofotherreceptors(includingghrelin),ionchannelsandenzymes.Inrabbitgastricantrum,Camicinal(GSK962040)300nmolL1-10μmolL1causedaprolongedfacilitationoftheamplitudeofcholinergicallymediatedcontractions,toamaximumof248±47%at3μmolL1.ThepEC50valuesformotilin,erythromycinandCamicinal(GSK962040)were,respectively,10.4±0.01(n=770),7.3±0.29(n=4)and7.9±0.09(n=17)[1].Camicinal(GSK962040)activatedthedogmotilinreceptor(pEC505.79;intrinsicactivity0.72,comparedwith[Nle13]-motilin)[2].Camicinal(GSK962040)waspreferredbecauseitsinitialIC50valuesatCYP3A4weresignificantlyhigherthanourpreferredthresholdof10μM[3].體內(nèi)研究Camicinal(GSK962040)(5mgfreebasekg1)alsoproducedanincreaseintotalfaecalweightoverthe2-hpostdoseperiod(21.2±4.5g;P<0.05)[1].Camicinal(GSK962040)inducedphasiccontractions,thedurationofwhichwasdose-related(48and173minfor3and6mgkg1),drivenbymeanplasmaconcentrations>1.14μmolL1.AftertheeffectsofGSK962040faded,migratingmotorcomplex(MMC)activityreturned.Migratingmotorcomplexrestorationwasunaffectedby3mgkg1GSK962040butat6mgkg1,MMCsreturned253minafterdosing,comparedwith101minaftersaline(n=5each)[2].heoralbioavailability(Fpo)ofCamicinal(GSK962040)wasfoundtobe48(13%.Camicinal(GSK962040)showsalonglastingeffect(T1/2)46.9(5.0minat3μM)whencomparedwiththeshort-livedeffectof[Nle13]motilin(T1/2)11.4(1.5minat0.3μM)[3].Camicinal(GSK962040)stronglyfacilitatedcholinergicactivityintheantrum,withloweractivityinfundusandsmallintestineonly[4].戶使?本產(chǎn)品發(fā)表的科研?獻?Chromatographia.2017,80(8),12571262.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Sanger,G.J.,etal.,GSK962040:asmallmolecule,selectivemotilinreceptoragonist,effectiveasastimulantofhumanandrabbitgastrointestinalmotility.NeurogastroenterolMotil,2009.21(6):p.657-64,e30-1.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[2].Leming,S.,etal.,GSK962040:asmallmoleculemotilinreceptoragonistwhichincreasesgastrointestinalmotilityinconsciousdogs.NeurogastroenterolMotil,2011.23(10):p.958-e410.[3].Westaway,S.M.,etal.,DiscoveryofN-(3-fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine(GSK962040),thefirstsmallmoleculemotilinreceptoragonistclinicalcandidate.JMedChem,2009.52(4):p.1180-9.[4].Broad,J.,etal.,Regional-andagonist-dependentfacilitationofhumanneurogastrointestinalfunctionsbymotilinreceptoragonists.BrJPharmacol,2012.167(4):p.763-74.McePdf