Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECalhex231hydrochlorideCat.No.:HY-103320ACASNo.:2387505-78-2分?式:C??H??Cl?N?O分?量:443.41作?靶點(diǎn):CaSR作?通路:GPCR/GProtein儲(chǔ)存?式:-20°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:33.33mg/mL(75.17mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.2552mL11.2762mL22.5525mL5mM0.4510mL2.2552mL4.5105mL10mM0.2255mL1.1276mL2.2552mL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(sealedstorage,awayfrommoisture)。-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.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(5.64mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.64mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性Calhex231hydrochloride?種通過(guò)負(fù)變構(gòu)調(diào)節(jié)來(lái)抑制CaSR的。Calhex231hydrochloride在HEK293細(xì)胞中阻斷Ca2+誘導(dǎo)的肌醇磷酸酯的積累，IC50為0.39μM。Calhex231hydrochloride可?于糖尿病性?肌病(DCM)的研究。IC50&TargetCaSR[1]IC50:0.39μM(Inositolphosphate)[2]體外研究Calhex231treatmentsignificantlydecreasestheproliferationofcardiacfibroblasts[1].Calhex231treatmentsignificantlydownregulatestheCaSR,α-SMA,Col-I/III,MMP2/9expresses.Calhex231alleviateshighglucose-inducedmyocardialfibrosisincardiacfibroblasts[1].Calhex231couldinhibitItch(atrophin-1interactingprotein4)-ubiquitinproteasomeandTGF-β1/Smadspathways,andthendepresstheproliferationofcardiacfibroblasts,alongwiththereductiondepositionofcollagen,alleviateglucose-inducedmyocardialfibrosis[1].CellProliferationAssay[1]CellLine:Primaryneonatalratcardiacfibroblasts(CFs)Concentration:3μMIncubationTime:24hoursResult:Significantlydecreasedtheproliferationofcardiacfibroblasts.WesternBlotAnalysis[1]CellLine:Primaryneonatalratcardiacfibroblasts(CFs)Concentration:3μMIncubationTime:48hoursResult:TheexpressionofCaSR,α-SMA,Col-I/III,MMP2/9weresignificantlydownregulated.體內(nèi)研究Calhex231(4.07mg/kg(10μmol/kg);intraperitonealinjection;daily;for12weeks;maleWistarrats)treatmentamelioratesdiabeticmyocardialfibrosisintype1diabeticmodel(T1D)rats[1].AnimalModel:MaleWistarrats(8weeksold)injectedwithStreptozotocin[1]Dosage:4.07mg/kg(10μmol/kg)Administration:Intraperitonealinjection;daily;for12weeksResult:AmeliorateddiabeticmyocardialfibrosisinT1Drats.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?FrontPharmacol.2022Feb23;13:816133.?FrontPharmacol.23February2022.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YuanH,etal.Calhex231AlleviatesHighGlucose-InducedMyocardialFibrosisviaInhibitingItch-UbiquitinProteasomePathwayinVitro.BiolPharmBull.2019Aug1;42(8):1337-1344.[2].PetrelC1,etal.ModelingandmutagenesisofthebindingsiteofCalhex231,anovelnegativeallostericmodulatoroftheextracellularCa(2+)-sensingreceptor.JBiolChem.2003Dec5;278(49):49487-94.McePdfHeightCaution:Producthasnotbe