AS-99-TFA-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAS-99TFACat.No.:HY-141429A分?式:C??H??F?N?O?S?分?量:707.71作?靶點:HistoneMethyltransferase;Apoptosis作?通路:Epigenetics;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:250mg/mL(353.25mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.4130mL7.0650mL14.1301mL5mM0.2826mL1.4130mL2.8260mL10mM0.1413mL0.7065mL1.4130mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.94mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.94mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性AS-99TFA?創(chuàng)的、有效的、選擇性的ASH1L組蛋?甲轉(zhuǎn)移酶抑制劑(IC50=0.79μM,Kd=?0.89?μM)，具有抗??病活性。AS-99TFA在體內(nèi)阻斷細胞增殖，誘導細胞凋亡(apoptosis)和分化，下調(diào)MLL融合靶因，減輕??病。IC50&Target0.79?μM(ASH1Lhistonemethyltransferase)[1]體外研究AS-99TFAistestedagainstapanelof20histonemethyltransferases,includingNSD1,NSD2,NSD3,andSETD2.NOsignificantinhibitionisobservedat50?μMofAS-99TFAonanyofthetestedhistonemethyltransferases,indicatingover100-foldselectivitytowardsASH1L[1].AS-99showsaseveralfoldweakereffectontheproliferationofleukemiacellswithoutMLL1translocations,suchasSET2andK562,withnoorlimitedeffectsat10?μMorhigherconcentrations[1].AS-99(1-8μM;7days)TFAalsoinducesapoptosisintheMLLleukemiacells,butnotintheK562cells,asassessedbythequantificationoftheAnnexinVpositivecells[1].AS-99TFAsuppressesMLLfusiondriventranscriptionalprograms[1].AS-99resultsinareducednumberofH3K36me2peakswhencomparedtotheDMSO-treatedcells[1].RT-PCR[1]CellLine:MOLM13cellsConcentration:2-6μMIncubationTime:7daysResult:Ledtoadose-dependentdownregulationofcanonicalMLLfusiontargetgenesrequiredforleukemogenesisincludingMEF2C,DLX2,FLT3,andHOXA9.體內(nèi)研究AS-99(30?mg/kg;i.p.;q.d.,treatedfor14consecutivedays)TFAreducesleukemiaburdeninmice[1].AS-99TFAisusedforinvivostudiesinmice,whichrevealsfavorableexposureinplasmauponi.v.andi.p.administration(AUC?=?9701?hr*ng/mLand10,699?hr*ng/mL,respectively),suitablehalf-life(~5–6?h)andCmax?>10?μM[1].AnimalModel:8-to10-weekoldfemaleNSGmice(bearingMV4;11cells)[1]Dosage:30?mg/kgAdministration:I.p.;q.d.,treatedfor14consecutivedaysResult:ReducedtheleukemiaburdeninthexenotransplantationmousemodelofMLLleukemiawithoutaffectingbloodcountsinnormalmice.REFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].DavidS.Rogawski,JingDeng,HaoLi,TomaszCierpicki,JolantaGrembecka,etal.Discoveryoffirst-in-classinhibitorsofASH1Lhistonemethyltransferasewithanti-leukemicactivity.NatCommun.2021May14;12(1):2792.McePdfHeightCaution:Producthasnotbeenfully