Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEUzansertibphosphateCat.No.:HY-101870BCASNo.:2088852-47-3Synonyms:INCB053914phosphate分?式:C??H??F?N?O?P分?量:611.51作?靶點(diǎn):Pim作?通路:JAK/STATSignaling儲(chǔ)存?式:4°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:5mg/mL(8.18mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.6353mL8.1765mL16.3530mL5mM0.3271mL1.6353mL3.2706mL10mM---------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:≥1.8mg/mL(2.94mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.8mg/mL(2.94mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.8mg/mL(2.94mM);ClearsolutionBIOLOGICALACTIVITY?物活性Uzansertib(INCB053914)phosphate?種具有?服活性的，ATP競(jìng)爭(zhēng)性泛-PIM激酶抑制劑，對(duì)于PIM1，PIM2和PIM3的IC50分別為0.24nM，30nM和0.12nM。Uzansertibphosphate對(duì)多種?液腫瘤細(xì)胞系具有?泛的抗增殖活性。IC50&TargetPIM1PIM2PIM30.24nM(IC50)30nM(IC50)0.12nM(IC50)體外研究Uzansertibphosphateinhibitsproliferationinallmultiplemyeloma(MM)celllinestested,withmeanGI50valuesrangingfrom13.2nMto230.0nMinAML,MM,DLBCL,MCL,andT-ALLcelllines[1].Uzansertibphosphate(0.1,0.3,1,3,10,30,100,300,1000nM)inhibitsthephosphorylationofdownstreamPIMkinasesubstrates(p70S6K/S6and4E-BP1)inadose-dependentmannerinMOLM-16(AML),Pfeiffer(DLBCL),andKMS-12-PE/BM(MM)celllines[1].PIMkinase-mediatedphosphorylationofBADinMOLM-16andKMS-12-BMcellsisparticularlysensitivetoinhibitionbyUzansertibphosphate(meanIC50,4nMand27nM,respectively)[1].體內(nèi)研究Uzansertibphosphate(25-100mg/kg;PO;twiceaday;for15days)inhibitstumorgrowthinadose-dependentmannerinmicebearingMOLM-16(AML)orKMS-12-BM(MM)[1].Uzansertibphosphatedemonstratesadose-dependentinhibitionofBADphosphorylationrelativetovehicleat4hourspostdose(MOLM-16tumors,IC50=70nM;KMS-12-BMtumors,IC50=145nM)[1].AnimalModel:Femaleimmunecompromised(severecombinedimmunodeficiency[SCID])mice(5-9weeksofage)bearingMOLM-16(AML)orKMS-12-BM(MM)[1]Dosage:25,50,75,100mg/kgAdministration:PO;twiceaday;for15daysResult:Inhibitedtumorgrowthinadose-dependentmannerinmice.REFERENCES[1].KoblishH,etal.PreclinicalcharacterizationofINCB053914,anovelpan-PIMkinaseinhibitor,aloneandincombinationwithanticanceragents,inmodelsofhematologicmalignancies.PLoSOne.2018Jun21;13(6):e0199108.McePdfHeightCaution:Producthasnotbeenfullyvalidated