AG-270-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAG-270Cat.No.:HY-138630CASNo.:2201056-66-6分?式:C??H??N?O?分?量:489.57作?靶點(diǎn):Others作?通路:Others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:190mg/mL(388.10mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.0426mL10.2130mL20.4261mL5mM0.4085mL2.0426mL4.0852mL10mM0.2043mL1.0213mL2.0426mL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:≥4.25mg/mL(8.68mM);Clearsolution1/3MasterofBioactiveMolecules—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:0.71mg/mL(1.45mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥0.71mg/mL(1.45mM);ClearsolutionBIOLOGICALACTIVITY?物活性AG-270?競(jìng)爭(zhēng)性的、?創(chuàng)的、可逆的、具有?服活性的MAT2A變構(gòu)抑制劑，其IC50值為14nM。IC50&TargetIC50:14nM(MAT2A)[1].體外研究AG-270demonstratespotentreductioninlevelsofintracellularSAM,aswellasMTAP-null–selectiveantiproliferativeactivityintheHCT116MTAPisogeniccellmodelinvitro[1].AG-270exhibitsanIC50of20nMinHCT116MTAP-nullcellSAMat72h[1].MAT2Aisakeyenzymeinthemethioninesalvagepathway,responsibleforgeneratingtheuniversalmethyldonor,S-adenosylmethionine(SAM)[2].體內(nèi)研究AG-270showsexcellentmicrosomal,hepatocyte,andinvivometabolicstabilityacrossspecies(human,mouse,rat,dog,andmonkey).AG-270exhibitsT1/2valuesof5.9h,4.2h,4.8hand21.3hinmouse,rat,monkeyanddog,respectively[1].AG-270(200mg/kg,orally,q.d.for38days)resultsindose-dependentreductionintumorSAMlevelsandtumorgrowthofKP4MTAP-nullxenograftsandiswelltolerated,withmeanbodyweightloss[1].CombiningAG-270withtaxanesandgemcitabineyieldedadditive-tosynergisticantitumoractivity,withthedocetaxelcombinationyielding50%completetumorregressionsinselectmodels;combinationbenefitsareobservedinPDXmodelsderivedfromesophageal,NSCLC,andpancreaticcancers[2].AnimalModel:PancreaticKP4MTAP-nullxenograftmousemodel[1].Dosage:10-200mg/kg.Administration:Orally,q.d.for38days.Result:Ledtodose-dependentreductionsintumorSAMlevelsandtumorgrowthofKP4MTAP-nullxenografts(TGI=36%(10mg/kg),48%(30mg/kg),66%(100mg/kg),67%(200mg/kg).戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?FASEBJ.2022Feb;36(2):e22167.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].ZenonKonteatis,etal.DiscoveryofAG-270,aFirst-in-ClassOralMAT2AInhibitorfortheTreatmentofTumorswithHomozygousMTAPDeletion.JMedChem.2021Apr8.[2].MarcLHyer,etal.TheMAT2AinhibitorAG-270combineswithbothtaxanesandgemcitabinetoyieldenhancedantitumoractivityinpatient-derivedxenograftmodels.McePdfHeightCaution:Producthasnotbeenfullyv