TC-G-1008-GPR39-C3-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETC-G-1008Cat.No.:HY-103007CASNo.:1621175-65-2Synonyms:GPR39-C3分⼦式:C₁₈H₁₉ClN₆O₂S分⼦量:418.9作⽤靶点:GHSR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(238.72mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3872mL11.9360mL23.8720mL5mM0.4774mL2.3872mL4.7744mL10mM0.2387mL1.1936mL2.3872mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.97mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.97mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.97mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性TC-G-1008(GPR39-C3)有效的，有⼝服活性的GPR39激动剂，对⼤⿏和⼈类受体的EC50值分别为0.4和0.8nM。IC50&TargetIC50:0.4nM(GPR39),0.8nM(GPR39)[1]体外研究TC-G-1008showsselectivityoverapanelofkinases(IC50s>10μM)anddoesnotexhibitrelevantbindingaffinityfortherelatedghrelinandneurotensin-1receptors(IC50s>30μM)[1].InHEK293-GPR39cells,GPR39-C3,whichisapositiveallostericmodulator,activatescAMPproduction(downstreamofGs),IP1accumulation(downstreamofGq),SRF-RE-dependenttranscription(downstreamofG12/13),andβ-arrestinrecruitment.GPR39-C3inducesdose-andtime-dependentlossofresponseincAMPproductionbysecondchallengeofthecompound[2].体内研究RatandmouseplasmaproteinbindingforTC-G-1008ismeasuredas99.3%and99.1%,respectively.TC-G-1008isorallybioavailableinmiceandrobustlyinducesacuteGLP-1levels.Uponsingleoraldosesof10,30,and100mg/kgofaqueoussuspensionsin0.5%methylcellulose/0.1%Tween80,TC-G-1008achieves,between1and1.5h,maximalexposuresof1.4,6.1,and25.3μM,respectively[1].PROTOCOLKinaseAssay[2]HEK293-GPR39cellsareplatedandculturedinpoly-d-lysine-coated,white,384-wellplates(4000cells/well)inthegrowthmediumovernightat37°Cinthepresenceof5%CO2.ForpretreatmentofthecellswithGPR39ligands(TC-G-1008)orvehiclecontrol(DMSO),theculturemediumisremovedandthecellsarestimulatedwithGPR39ligandsinassaybufferfortheindicatedtimeat37°C.Then,thecompoundsolutionisremovedandwashedtwicewithPBScontaining0.1%BSA.FormeasurementofintracellularcAMP,thecellsarestimulatedwithdrugsinstimulationbufferfor30minat37°C.TheintracellularcAMPlevelisdeterminedbyusingHTRFcAMPdynamic2kit[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Micearegivensingleoraldosesof10,30,and100mg/kgofTC-G-1008[1].Administration[1]MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].PeukertS,etal.Discoveryof2-PyridylpyrimidinesastheFirstOrallyBioavailableGPR39Agonists.ACSMedChemLett.2014Aug4;5(10):1114-8.[2].ShimizuY,etal.Rhokinase-dependentdesensitizationofGPR39;auniquemechanismofGPCRdownregulation.BiochemPharmacol.2017Sep15;140:105-114.McePdfHeightCaution:Product