Camicinal-GSK962040-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECamicinalCat.No.:HY-10922CASNo.:923565-21-3Synonyms:GSK962040分⼦式:C₂₅H₃₃FN₄O分⼦量:424.55作⽤靶点:MotilinReceptor作⽤通路:GPCR/GProtein储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(235.54mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3554mL11.7772mL23.5544mL5mM0.4711mL2.3554mL4.7109mL10mM0.2355mL1.1777mL2.3554mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.89mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.89mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.89mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Camicinal(GSK962040)胃动素受体激动剂，pEC50为7.9。IC50&TargetpEC50:7.9(MotilinReceptor)[1].体外研究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].体内研究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].户使⽤本产品发表的科研⽂献•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—您⾝边的抑制剂⼤师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