Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBGC0222Cat.No.:HY-P10783分?式:C????H????N??O???分?量:26927.36作?靶點:Peptide-DrugConjugates(PDCs);Integrin作?通路:Antibody-drugConjugate/ADCRelated;Cytoskeleton儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性BGC0222?種新型Irinotecan(HY-16562)原藥。BGC0222作為?種PEG-cRGD偶聯(lián)的Irinotecan(HY-16562)衍?物，可緩慢、穩(wěn)定地釋放Irinotecan(HY-16562)。BGC0222與αVβ3靶點結(jié)合，其IC50值為4.25μM，針對αVβ5的IC50為58.7μM。BGC0222可誘導?管新?。BGC0222在多種腫瘤中表現(xiàn)出良好的抗腫瘤活性[1]。體外研究BGC0222(72h)exhibitsbetterantiproliferationactivitythanIrinotecan(HY-16562)andNKTR-102againstHT29,MIAPaCa-2andMCF-7tumorcelllines,withIC50of1.83??μM,3.95??μMand0.68??μM,respectively[1].BGC0222(40μM)showsgoodangiogenesisactivity,withthelengthofbloodvesselsof1930?mm(CAMangiogenesisassay)[1].體內(nèi)研究BGC0222(20-60mg/kg,i.v.,every4daysoronceaweek,3times)exhibitsremarkableantiproliferationactivityintheHT-29,MIAPaCa-2,NCI-H446,U-87?MGandMDA-MB-231xenograftnudemice,withlowerRTVandT/CvaluesthanthatofIrinotecan(HY-16562).BGC0222(30-90mg/kg,i.v.,onceweeklyfora28-dayperiod)improvessafetyprofilerelativetoirinotecanininSprague-Dawleyrats,withthemaximumtolerateddose(MTD)of90?mg/kgandlessthan60?mg/kg,respectively[1].BGC0222(20-80mg/kg,i.v.,single)slowlyandsteadilyreleaseirinotecaninSprague-Dawleyrats[1].AnimalModel:HT-29,MIAPaCa-2,NCI-H446,U-87?MGandMDA-MB-231xenograftfemaleBalb/cnudemice(HT-29,4?×?106;MIAPaCa-2,5?×?106;NCI-H446,8?×?106;U-87?MG,4?×?106;MDA-MB-231,3?×?106)[1]Dosage:20mg/kg(MIAPaCa-2,NCI-H446,MDA-MB-231);40mg/kg(HT-29);60mg/kg(U-1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE87?MG)Administration:Intravenousinjection(i.v.),every4days(HT-29andMDA-MB-231)oronceaweek(MIAPaCa-2,NCI-H446andU-87?MG),3timesResult:ExhibitedremarkableantiproliferationactivityintheHT-29,MIAPaCa-2,NCI-H446,U-?87?MGandMDA-MB-231xenograftnudemice.ExhibitedthatT/CvaluesofBGC0222fordays12,15,18,22,25,29and32weredeterminedtobe100%,88.8%,57.0%,27.6%,16.9%,9.87%and9.21%,whilethatofirinotecanwerefoundtobe100%,103%,93.1%,75.1%,68.8%,60.6%,71.1%intheHT-29xenograftnudemice,respectively.ShowedthattheRTVvaluesofBGC0222weremuchlowerthanthatofirinotecanandNKTR-102whentheaveragetumorsizereachedapproximately100–300?mm3(afterday12)intheHT-29xenograftnudemice.REFERENCES[1].HuangYQ,etal.Design,synthesisandpharmacologicalevaluationofanovelPEG-cRGD-conjugatedirinotecanderivativeaspotentialantitumoragent.EurJMedChem.2018Oct5,158:82-90.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical