BGP-15-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBGP-15Cat.No.:HY-100828CASNo.:66611-37-8分⼦式:C₁₄H₂₄Cl₂N₄O₂分⼦量:351.27作⽤靶点:PARP作⽤通路:CellCycle/DNADamage;Epigenetics储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验H2O:100mg/mL(284.68mM;Needultrasonic)DMSO:11.33mg/mL(32.25mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.8468mL14.2341mL28.4681mL5mM0.5694mL2.8468mL5.6936mL10mM0.2847mL1.4234mL2.8468mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(7.12mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(7.12mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.12mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性BGP-15⼀种PARP抑制剂，IC50和Ki值分别为120和57μM。IC50&TargetPARP120μM(IC50)体外研究BGP-15(200μM)preventstheimatinibmesylate-inducedoxidativedamages,attenuatesthedepletionofhigh-energyphosphates,altersthesignalingeffectofimatinibmesylatebypreventingp38MAPkinaseandJNKactivation,andinducedthephosphorylationofAktandGSK-3beta[5].体内研究BGP-15(15mg/kg,p.o.)doesnotimproveskeletalmusclepathologyinoldermdxmice[1].Inaratmodel,10daysofBGP-15treatmentgreatlyimprovesdiaphragmmusclefiberfunction(byabout100%),althoughitdoesnotreversediaphragmatrophy.ThetreatmentalsoprovidesprotectionfrommyosinPTMsassociatedwithHSP72inductionandPARP-1inhibition,resultinginimprovementofmitochondrialfunctionandcontent[2].BGP-15(15mg/kgperdayinsaline)treatmenthasnoeffectinNtgmiceoranindependentcohortofnormaladultwild-typemicebasedonmorphology,cardiacfunctionandECGparameters.TreatmentwithBGP-15attenuatestheincreaseinatrialsizeandlungweight.BGP-15treatmentisabletopreventorreduceepisodesofarrhythmia.BGP-15treatmentisassociatedwithareducedPRintervalintheHF+AFmodel[3].BGP-15(10and30mg/kg)increasesinsulinsensitivityby50%and70%,respectively,incholesterol-fedbutnotinnormalrabbits.After5daysoftreatmentwithBGP-15,theglucoseinfusionrateisincreasedinadose-dependentmanneringeneticallyinsulin-resistantGKrats.Themosteffectivedoseis20mg/kg,whichshowsa71%increaseininsulinsensitivitycomparedtocontrolgroup[4].PROTOCOLAnimalAdult(appr4month)maleHF+AFandNtgmiceareadministeredwithBGP-15(15mg/kgperdayinsaline)Administration[3]for4weeksbyoralgavageorremaineduntreated(oralgavagewithsalineornogavage).GavagewithsalinehasnoeffectonmorphologicalorfunctionalparametersintheHF+AFmodel.Therefore,untreatedmice(nogavage)andmiceadministeredsalinearecombinedandreferredtoasHF+AFcontrol.EchocardiographyandECGstudiesareperformedbeforeandaftertreatment.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•JMolMed(Berl).2019Aug;97(8):1183-1193.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEREFERENCES[1].KennedyTL,etal.BGP-15ImprovesAspectsoftheDystrophicPathologyinmdxanddkoMicewithDifferingEfficaciesinHeartandSkeletalMuscle.AmJPathol.2016Dec;186(12):3246-3260[2].SalahH,etal.Thechaperoneco-inducerBGP-15alleviatesventilation-induceddiaphragmdysfunction.SciTranslMed.2016Aug3;8(350):350ra10[3].SapraG,etal.Thesmall-moleculeBGP-15protectsagainstheartfailureandatrialfibrillationinmice.NatCommun.2014Dec9;5:5705[4].Literati-NagyB,etal.Improvementofinsulinsensitivitybyanoveldrugcandidate,BGP-15,indifferentanimalstudies.MetabSyndrRelatDisord.2014Mar;12(2):125-31[5].SarszegiZ,etal.BGP-15,aPARP-inhibitor,preventsimatinib-inducedcardiotoxicitybyactivatingAktandsuppressingJNKandp38MAPkinases.MolCellBiochem.2012Jun;365(1-2):129-37[6].SzabadosE,etal.BGP-15,anicotinicamidoximederivateprotectingheartfromischemiareperfusioninjurythroughmodulationofpoly(ADP-ribose)polymerase.BiochemPharmaco