TC-G-1008-GPR39-C3-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETC-G-1008Cat.No.:HY-103007CASNo.:1621175-65-2Synonyms:GPR39-C3分?式:C??H??ClN?O?S分?量:418.9作?靶點(diǎn):GHSR作?通路:GPCR/GProtein儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥100mg/mL(238.72mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.3872mL11.9360mL23.8720mL5mM0.4774mL2.3872mL4.7744mL10mM0.2387mL1.1936mL2.3872mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)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(chǔ)備液可以根據(jù)儲(chǔ)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.97mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.97mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.97mM);ClearsolutionBIOLOGICALACTIVITY?物活性TC-G-1008(GPR39-C3)有效的，有?服活性的GPR39激動(dòng)劑，對(duì)??和?類受體的EC50值分別為0.4和0.8nM。IC50&TargetIC50:0.4nM(GPR39),0.8nM(GPR39)[1]體外研究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].體內(nèi)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?邊的抑制劑?師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