Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEH3B-5942Cat.No.:HY-112611CASNo.:2052128-15-9分?式:C??H??N?O?分?量:494.63作?靶點(diǎn):EstrogenReceptor/ERR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:83.33mg/mL(168.47mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.0217mL10.1086mL20.2171mL5mM0.4043mL2.0217mL4.0434mL10mM0.2022mL1.0109mL2.0217mL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%salineSolubility:≥2.08mg/mL(4.21mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.21mM);ClearsolutionBIOLOGICALACTIVITY?物活性H3B-5942?種選擇性、不可逆、可?服的estrogenreceptor共價(jià)拮抗劑，能夠靶作?于Cys530，使野?型和突變型ERα失活，Ki值分別為1nM和0.41nM。H3B-5942能夠減少ERα的?標(biāo)因GREB1的表達(dá)。H3B-5942具有抗癌作?，對(duì)含有ERαWT或者突變型ERα的腫瘤細(xì)胞和動(dòng)物具有抗腫瘤活性[1]。IC50&TargetERαY537SERαWT0.41nM(Ki)1nM(Ki)體外研究H3B-5942isaselectiveandirreversibleestrogenreceptorcovalentantagonist,inactivatesbothwild-typeandmutantERαbytargetingCys530,withKisof1nMand0.41nM,respectively[1].H3B-5942elevatesERαproteinleveldistinctfromSERMs/SERD,blocksERα-dependenttranscriptioninbreastcancercells.H3B-5942(0.01-10μM)reducesERαtargetgeneGREB1inMCF7-ERαWT,variousMCF7-ERαMUTlines,andthePDX-ERαY537S/WTline[1].H3B-5942alsodecreasesproliferationofMCF7-Parental,MCF7-LTED-ERαWT,andMCF7-LTED-ERαY537ClineswithGI50sof0.5,2,and30nM,respectively.H3B-5942(10-25nM)incombinationwithCDK4/6inhibitors(≥25pM)hassynergicinhibitoryeffectonmultiplecelllinesbearingERαWTorclinicallyfrequentERαmutations[1].體內(nèi)研究H3B-5942(1,3,10,or30mg/kg,p.o,q.d.for17days)dose-dependentlyinhibitstumorgrowthinMCF7xenograftmodelinathymicfemalenudemice[1].H3B-5942(3,10,30,100,and200mg/kg,p.o,q.d.)exhibitssimilaranti-tumoractivityintheERαY537S/WTST941modelinathymicfemalenudemice[1].AnimalModel:MCF7xenograftmodelinathymicfemalenudemice[1]Dosage:1,3,10,or30mg/kgAdministration:P.O.onceaday(q.d.×1)for17daysResult:Exhibitedtumorgrowthinhibition(TGI)onday17of19%,41%,68%,and83%,respectively.REFERENCES[1].PuyangX,etal.DiscoveryofSelectiveEstrogenReceptorCovalentAntagonistsfortheTreatmentofERαWTandERαMUTBreastCancer.CancerDiscov.2018Sep;8(9):1176-1193.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical