Torkinib-PP-242-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETorkinibCat.No.:HY-10474CASNo.:1092351-67-1Synonyms:PP242分?式:C??H??N?O分?量:308.34作?靶點(diǎn):mTOR;Autophagy;Mitophagy;Apoptosis作?通路:PI3K/Akt/mTOR;Autophagy;Apoptosis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:50mg/mL(162.16mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2432mL16.2159mL32.4317mL5mM0.6486mL3.2432mL6.4863mL10mM0.3243mL1.6216mL3.2432mL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%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(8.11mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(8.11mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.11mM);ClearsolutionBIOLOGICALACTIVITY?物活性Torkinib(PP242)?種選擇性，ATP競(jìng)爭(zhēng)型的mTOR抑制劑，IC50為8nM。PP242抑制mTORC1和mTORC2的IC50分別為30nM和58nM。IC50&TargetmTORC1mTORC2mTORp110δ30nM(IC50)58nM(IC50)8nM(IC50)100nM(IC50)DNA-PKPDGFRp110αp110β410nM(IC50)410nM(IC50)2μM(IC50)2.2μM(IC50)p110γAblHckScr1.3μM(IC50)3.6μM(IC50)1.2μM(IC50)1.4μM(IC50)Scr(T338I)VEGFR2EGFREphB45.1μM(IC50)1.5μM(IC50)4.4μM(IC50)3.4μM(IC50)AutophagyMitophagy體外研究Torkinib(PP242)potentlyinhibitsmTOR(IC50=8nM)butismuchlessactiveagainstotherPI3Kfamilymembers.TestingofTorkinib(PP242)against219proteinkinasesrevealsremarkableselectivityrelativetotheproteinkinome:ataconcentration100-foldaboveitsIC50formTOR,Torkinib(PP242)inhibitsonlyonekinasebymorethan90%(Ret)andonlythreebymorethan75%(PKCα,PKCβIIandJAK2V617F)[1].Torkinib(PP242)hasadose-dependenteffectonproliferationandathigherdosesismuchmoreeffectivethanRapamycinatblockingcellproliferation.TheabilityofTorkinib(PP242)toblockcellproliferationmoreefficientlythanRapamycincouldbearesultofitsabilitytoinhibitmTORC1andmTORC2,becauseRapamycincanonlyinhibitmTORC1.InSIN1-/-mouseembryonicfibroblasts(MEFs),RapamycinisalsolesseffectiveatblockingcellproliferationthanTorkinib.ThatTorkinib(PP242)andRapamycinexhibitverydifferentanti-proliferativeeffectsinSIN1-/-MEFssuggeststhatthetwocompoundsdifferentiallyaffectmTORC1[2].體內(nèi)研究Infatandliver,Torkinib(PP242)isabletocompletelyinhibitthephosphorylationofAktatS473andT308,consistentwithitseffectonthesephosphorylationsitesobservedincellculture.Surprisingly,Torkinib(PP242)isonlypartiallyabletoinhibitthephosphorylationofAktinskeletalmuscleandismoreeffectiveatinhibitingthephosphorylationofT308thanS473,despiteit'sabilitytofullyinhibitthephosphorylationof4EBP1andS6.Theseresultswillbeconfirmedbyinvivodose-responseexperiments,but,consistentwiththepartialeffectofTorkinib(PP242)onpAktinskeletalmuscle,amuscle-specificknockoutoftheintegral2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEmTORC2componentrictorresultedinonlyapartiallossofAktphosphorylationatS473.TheseresultssuggestthatakinaseotherthanmTOR,suchasDNA-PK,maycontributetophosphorylationofAktinmuscle[2].PROTOCOLCellAssay[2]Wild-typeandSIN1-/-MEFsareplatedin96-wellplatesatapproximately30%confluenceandleftovernighttoadhere.ThefollowingdaycellsaretreatedwithTorkinib(PP242)(1nM,10nM,100nM,1μM,and10μM),Rapamycin,orvehicle(0.1%DMSO).After72hoftreatment,10μLof440μMresazurinsodiumsaltisaddedtoeachwell,andafter18h,theflorescenceintensityineachwellismeasuredusingatop-readingflorescentplatereaderwithexcitationat530nmandemissionat590nm[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]Six-wk-oldmaleC57BL/6micearefastedovernightpriortodrugtreatment.Torkinib(PP242)(0.4mg),Rapamycin(0.1mg),orvehiclealoneisinjectedIP.After30minfortheRapamycin-treatedmouseor10minfortheTorkinib(PP242)andvehicle-treatedmice,250mUofinsulinin100μLofsalineisinjectedIP.15minaftertheinsulininjection,themicearekilledbyCO2asphyxiationfollowedbycervicaldislocation.Tissuesareharvestedandfrozenonliquidnitrogenin200μLofcaplysisbuffer.Thefrozentissueisthawedonice,manuallydisruptedwithamortarandpestle,andthenfurtherprocessedwithamicrotissue-homogenizer.ProteinconcentrationoftheclearedlysateismeasuredbyBradfordassayand5-10μgofproteinisanalyzedbyWesternblot[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ActaPharmSinB.2020Jun;10(6):1004-1019.?CancerRes.2013Apr15;73(8):2574-86.?JExpClinCancerRes.2021Jan9;40(1):25.?Theranostics.2022Jan1;12(2):675-688.?BreastCancerRes.2020Jun3;22(1):59.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ApselB,etal.Targetedpolypharmacology:discoveryofdualinhibitorsoftyrosineandphosphoinositidekinases.NatChemBiol.2008Nov;4(11):691-9.[2].FeldmanME,etal.Active-siteinhibitorsofmTORtargetrapa