Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPF-06869206Cat.No.:HY-112065CASNo.:2227425-05-8分?式:C??H??ClF?N?O?分?量:374.75作?靶點(diǎn):SodiumChannel作?通路:MembraneTransporter/IonChannel儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(266.84mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6684mL13.3422mL26.6845mL5mM0.5337mL2.6684mL5.3369mL10mM0.2668mL1.3342mL2.6684mL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(fù)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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(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?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.67mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.67mM);ClearsolutionBIOLOGICALACTIVITY?物活性PF-06869206?種有效的，具有?服活性的選擇性磷酸鈉協(xié)同轉(zhuǎn)運(yùn)蛋?NaPi2a(SLC34A1)抑制劑，IC50為380nM[1]。IC50&TargetIC50:380nM(NaPi2a/SLC34A1)[1]體外研究PF-06869206showsabalanceofattributeswith380nMNaPi2ainhibitionpotency,excellentsubtypeselectivity,andacceptableaqueoussolubility(46μM).PF-06869206isprofiledforpotencyintherodentNaPi2aandNaPi2ccelllines.PF-06869206showscomparablesubmicromolaractivityforthehuman,rat,andmouseNaPi2aisoformswithIC50sof0.4±0.047μMand0.54±0.099μMforratNaPi2aandmouseNaPi2a,respectively[1].體內(nèi)研究PF-06869206isevaluatedinrodentPKstudiestodeterminesuitabilityforinvivopharmacologyexploration.Resultsshowmoderateclearanceinbothratandmouse.Oralbioavailabilityat5mg/kgisgoodinratandmoderateinmouse.Athigheroraldosesof50mg/kg,supraproportionalincreasesinexposureareobservedinbothspecies,suggestiveofsaturationofclearance.PF-06869206hasmoderateterminaleliminationhalf-life(t1/2=1.35h,and0.75hforWistar-Hanrats(10mg/kg,iv),andC57BL6mice(1mg/kg,iv)).Furthermore,permeabilityisgood(14×10-6cm/s),andratlivermicrosome(RLM)clearanceislow([1].PROTOCOLAnimalRatsandMice[1]Administration[1]MaleWistar-Hanrats(n=2)aretreatedwithPF-06869206(1mg/kg,5mg/kg,and50mg/kg;2mL/kgforivor10mL/kgforpo).C57BL6mice(n=2)aretreatedwithPF-06869206(1mg/kg,5mg/kg,and50mg/kg;2mL/kgforivor10mL/kgforpo)[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].FilipskiKJ,etal.DiscoveryofOrallyBioavailableSelectiveInhibitorsoftheSodium-PhosphateCotransporterNaPi2a(SLC34A1).ACSMedChemLett.2018Apr12;9(5):440-445.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedic