Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEOdafosfamideCat.No.:HY-149040CASNo.:2097713-69-2Synonyms:(S)-OBI-3424;(S)-TH-3424;AST-3424分子式:C??H??N?O?P分子量:460.42作用靶點:17β-HSD作用通路:MetabolicEnzyme/Protease儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Odafosfamide((S)-OBI-3424)是一種高選擇性的由醛酮還原酶1C3(AKR1C3)激活的前體藥物雙烷化劑。Odafosfamide對AKR1C3表達高的細胞系具有有效的細胞毒性。Odafosfamide在多種高表達AKR1C3的腫瘤(如肝癌、非小細胞肺癌、白血病)中表現(xiàn)出抗腫瘤活性。Odafosfamide可用于癌癥研究。體外研究Odafosfamide(72-96h)showscytotoxicityagainstlivercancercells(SNU-475,SNU-449,C3A,withIC50sof15nM,45nM,5nM,respectively)andnon-smallcelllungcancercells(NSCLC)(NCI-H1944,NCI-H2228,NCIH1755,NCI-H1563,NCI-H2110,NCI-H1792,withIC50sof2.3nM,0.21nM,8.2nM,2.5nM,1.1nM,4.5nM,respectively)withhighAKR1C3proteinandRNAexpressionlevels[1].Odafosfamideshowspotentanti-leukemicactivityagainst19leukemiacelllinesrepresentingB-ALL,T-ALL,andETP-ALL(IC50svalueswere60.3nmol/L,9.7nmol/L,and31.5nmol/L,respectively)[2].體內研究Odafosfamide(1.25-5mg/kg,i.v.,onceaweek,2weeks)inhibitstumorgrowthinHepG2orthotopicxenograftmodel[1].Odafosfamide(0.625-1.25mg/kg,i.v.,weeklyfor2cycles;withoneweekoff,andanother2cyclesofweekly)inhibitstumorgrowthinH460subcutaneousmodel[1].Odafosfamide(2.5mg/kg,5mg/kg,i.v.,weeklyfor4-5doses)inhibitstumorgrowthin(CRPC)VCaP,SNU-16andA498xenograftmodel[1].Odafosfamide(1.25-5mg/kg,i.v.,onceaweek,3weeks)inhibitstumorgrowthinPA1280,GA6201andLU2505xenograftmodel[1].Odafosfamide(2.5mg/kg,i.p.,onceweekly×3weeks)inducessubstantialandprolongedregressionsofdiseaseinPDXmodelsofpediatricALL[2].1/2 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEAnimalModel:HepG2orthotopicxenograft(~1mm3indiameter)femaleathymicnudemice(6weeks;BALB/c-nu)model[1]Dosage:1.25mg/kg,2.5mg/kg,5mg/kgAdministration:i.v.,onceaweek,2weeksResult:Inhibitedtumorgrowth,withgrowthinhibition(TGI)atDay34of52.4%at1.25mg/kg,91.5%at2.5mg/kgand101.2%at5mg/kg,respectively.AnimalModel:(CRPC)VCaPxenograftmaleBALB/cnudemicemodel[1]Dosage:2.5mg/kg,5mg/kgAdministration:i.v.,weeklyfor5dosesResult:Inhibitedtumorgrowth,withgrowthinhibitionof148%at5mg/kg,furtherenhancedto158%whencombinedwithAbiraterone(HY-70013)/Prednisolone(HY-17463).AnimalModel:PDX(female20–25g)NSGmicemodelsofpediatricALL[2]Dosage:2.5mg/kgAdministration:i.p.,onceweekly×3weeksResult:InducedsubstantialandprolongedregressionsofdiseaseinAll-8,ALL-27,ALL-29,ALL-30,ALL-31,ALL-28,ALL-AKR1C3,combinedwithNelarabine(HY-13701)resultedinprolongationofmouseEFScomparedwitheachsingleagentalone.REFERENCESMengF,etal.AnovelselectiveAKR1C3-activatedprodrugAST-3424/OBI-3424exhibitsbroadanti-tumoractivity.AmJCancerRes.2021Jul15;11(7):3645-3659.EvansK,etal.OBI-3424,aNovelAKR1C3-ActivatedProdrug,ExhibitsPotentEfficacyagainstPreclinicalModelsofT-ALL.ClinCancerRes.2019Jul15;25(14):4493-4503.McePdfHeightCaution:Producthasnotbeenfullyva