HPK1-IN-7-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEHPK1-IN-7Cat.No.:HY-138742CASNo.:2320462-65-3分?式:C??H??N?O?分?量:458.47作?靶點(diǎn):MAP4K作?通路:MAPK/ERKPathway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:125mg/mL(272.65mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1812mL10.9058mL21.8117mL5mM0.4362mL2.1812mL4.3623mL10mM0.2181mL1.0906mL2.1812mL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.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.54mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性HPK1-IN-7?種有效的?服活性HPK1(造?祖細(xì)胞激酶1,MAP4K1)抑制劑(IC50=2.6nM)，具有優(yōu)良的家族和激酶組選擇性。HPK1-IN-7對(duì)IRAK4(59nM)和GLK(140nM)具有選擇性。HPK1-IN-7聯(lián)合抗PD1對(duì)MC38同因腫瘤模型顯?出強(qiáng)?的療效。IC50&TargetHPK1GLK/MAP4K3IRAK4Fms/CSFR2.6nM(IC50)140nM(IC50)59nM(IC50)3.2nM(IC50)FLT3AMPKA1cKITMST125.4nM(IC50)44.3nM(IC50)45.7nM(IC50)55.1nM(IC50)ICKMST265.1nM(IC50)78.5nM(IC50)體內(nèi)研究HPK1-IN-7(100mg/kg;p.o.;twicedailyfor28days)showsrobustenhancementofanti-PD1efficacyinasyngeneictumormodelofcolorectalcancer[1].HPK1-IN-7(compound24)(1mg/kg;intravenous;mice)ischaracterizedbymoderateplasmaclearance(43mL/min/kg)andalargevolumeofdistribution(4.4L/kg).Afteroraladministration(20mg/kg),theCmaxwas5.3μMandtheAUC0-24hwas19μM?h.Thecalculatedoralbioavailabilitybasedonthesepharmacokineticsstudiesisapproximately100%[1].AnimalModel:Mice(MC38syngeneictumormodel)[1]Dosage:100mg/kgAdministration:Oral;twicedailyfor28daysResult:Enhancedtheefficacyofanti-PD1treatment,garneringa100%cureratevsa20%cureratewithanti-PD1alone.REFERENCES[1].DegnanAP,etal.DiscoveryofOrallyActiveIsofuranonesasPotent,SelectiveInhibitorsofHematopoeticProgenitorKinase1.ACSMedChemLett.2021;12(3):443-450.Published2021Feb19.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearch