BGP-15-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBGP-15Cat.No.:HY-100828CASNo.:66611-37-8分?式:C??H??Cl?N?O?分?量:351.27作?靶點(diǎn):PARP作?通路:CellCycle/DNADamage;Epigenetics儲(chǔ)存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)H2O:100mg/mL(284.68mM;Needultrasonic)DMSO:11.33mg/mL(32.25mM;Needultrasonicandwarming)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.8468mL14.2341mL28.4681mL5mM0.5694mL2.8468mL5.6936mL10mM0.2847mL1.4234mL2.8468mL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(sealedstorage,awayfrommoisture)。-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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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:≥2.5mg/mL(7.12mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(7.12mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.12mM);ClearsolutionBIOLOGICALACTIVITY?物活性BGP-15?種PARP抑制劑，IC50和Ki值分別為120和57μM。IC50&TargetPARP120μM(IC50)體外研究BGP-15(200μM)preventstheimatinibmesylate-inducedoxidativedamages,attenuatesthedepletionofhigh-energyphosphates,altersthesignalingeffectofimatinibmesylatebypreventingp38MAPkinaseandJNKactivation,andinducedthephosphorylationofAktandGSK-3beta[5].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?JMolMed(Berl).2019Aug;97(8):1183-1193.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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