BTK-inhibitor-17-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBTKinhibitor17Cat.No.:HY-131705CASNo.:1858206-76-4分?式:C??H??N?O?分?量:456.5作?靶點(diǎn):Btk作?通路:ProteinTyrosineKinase/RTK儲(chǔ)存?式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(219.06mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1906mL10.9529mL21.9058mL5mM0.4381mL2.1906mL4.3812mL10mM0.2191mL1.0953mL2.1906mL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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.48mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.48mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.48mM);ClearsolutionBIOLOGICALACTIVITY?物活性BTKinhibitor17?種有效的具有?服活性不可逆BTK抑制劑，IC50為2.1nM。BTKinhibitor17可?于類風(fēng)濕關(guān)節(jié)炎的研究。IC50&TargetIC50:2.1nM(BTK)[1]體外研究BTKinhibitor17(compound8)couldcovalentlybindtoCys481andformedanHBnetworkwithhingekeyresiduesMet477,Glu475,andgatekeeperThr474[1].體內(nèi)研究BTKinhibitor17(compound8;3-10mg/kg;oralgavage;daily;for28days)treatmentinhibitsthesignificantprogressionofthediseaseandexhibitsacleardose-dependentreductionperpawclinicalscores,andnosignificantbodyweightlossisobservedforalldifferentdosages[1].BTKinhibitor17(compound8)shows>95%plasmaproteinbindingacrossthreespeciesofhuman,rat,andmouse.Afteranintravenousinjection,thehalf-life(rat,0.32h;mice,0.42h),clearance(rat,54.6mL/min/kg;mice,31.3mL/min/kg),volumeofdistribution(rat,1.55L/kg;mice,0.82L/kg),andAUCexposure(rat,604ng.h/mL;mice,576ng.h/mL)areobservedintwospecies.Afteroraladministration,BTKinhibitor17exhibitshigherCmax(rat,466ng/mL;mice,252ng/mL)andplasmaexposure(rat,642ng.h/mL;mice,128ng.h/mL)withafavorableoralbioavailability(rat,23.7%;mice,11.2%)[1].AnimalModel:MaleBalb/Cmiceinjectedwithcollagen[1]Dosage:3mg/kgor10mg/kgAdministration:Oralgavage;daily;for28daysResult:Inhibitedthesignificantprogressionofthediseaseandexhibitedacleardose-dependentreductionperpawclinicalscores.REFERENCES[1].XuejunZhang,etal.DiscoveryandEvaluationofPyrazolo[3,4-d]pyridazinoneasaPotentandOrallyActiveIrreversibleBTKInhibitor.ACSMedChemLett.2019Dec11;11(10):1863-1868.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical