PD176252-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPD176252Cat.No.:HY-103286CASNo.:204067-01-6分⼦式:C₃₂H₃₆N₆O₅分⼦量:584.67作⽤靶点:BombesinReceptor作⽤通路:GPCR/GProtein储存⽅式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性数据体外实验DMSO:115mg/mL(196.69mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.7104mL8.5518mL17.1037mL5mM0.3421mL1.7104mL3.4207mL10mM0.1710mL0.8552mL1.7104mL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(storedundernitrogen)。-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:5.75mg/mL(9.83mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥5.75mg/mL(9.83mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性PD176252⼀种有效的BB1和BB2拮抗剂，能够抑制⼈BB1和BB2受体和⼤⿏BB1和BB2受体活性，Ki值分别为0.17nM，1nM和0.66nM，16nM；PD176252同时为FPR1/FPR2的激动剂，在HL-60细胞中，EC50值分别为0.31和0.66μM。IC50&TargetKi:0.17nM(HumanBB1receptor),0.66nM(RatBB1receptor),1nM(HumanBB2receptor),16nM(RatBB2receptor)[1]EC50:0.31μM(FPR1),0.66μM(FPR2)[2]体外研究PD176252isapotentantagonistofneuromedin-Bpreferring(BB1)andgastrin-releasingpeptide-preferring(BB2)receptorwithKisof0.17nMand1nMforhumanBB1andBB2receptors,and0.66nM,16nMforRatBB1andBB2receptors,respectively.PD176252inhibitsacidificationresponsestoneuromedin-Borneuromedin-CatthehumanBB1orBB2receptorsexpressedinCHOcells,withtheappKBsof4.0nMor13nM,andblocksbombesin-evokedincreasesinintracellularcalciumlevelsinCHOcellsstablyexpressinghumanBB1orBB2receptors,withappKBsof2.3nMand36nM,respectively.PD176252isalsoanagonistofN-Formylpeptidereceptor1/2(FPR1/FPR2),withEC50sof0.31and0.66μMinHL-60cells.PD176252activatesCa2+mobilizationinHL-60cellstransfectedwithhumanFPRs(EC50,0.72±0.21μM)[2].PD176252inhibitslittlespecific125I-gastrinreleasingpeptidebindingtoNCI-H345cellsat1nMandsuppressesalmostallspecificbindingsat1000nM,withanIC50of30nM.PD176252(10,30μM)significantlyinhibitsthegrowthofNCI-H345orH1299cells,withIC50sof7and5μM[3].体内研究PD176252(1,10μg,p.o.)potentlyinhibitsthegrowthoftheproliferationofNCI-H1299xenograftsinnudemice[3].PROTOCOLCellAssay[3]GrowthstudiesinvitroareconductedusingtheMTTcolorimeticassays.NCI-H1299cells(104/well)areplacedinSITmediumandvariousconcentrationsofPD176252orPD168368added.After4days,MTTisadded.After4h,150μLofDMSOisadded.After16h,theopticaldensityat570nmisdetermined[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]FemaleathymicBalb/cnudemice,4-5weeksold,arehousedinapathogen-freetemperaturecontrolledisolationroom,withadietconsistingofautoclavedrodentchowandautoclavedwatergivenadlibitum.NCI-H1299cells(1×107)areinjectedintotherightflankofeachmousebysubcutaneousinjection.Palpabletumorsareobservedinapproximately90%ofthemiceafter1week.Polyethyleneglycol(PEG,100μL)orPD176252(10or1μgin100μLofPEG400)areinjecteddailybygavage.Thetumorvolume(height×width×depth)isdeterminedweeklybycalipersandrecorded[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].AshwoodV,etal.PD176252--thefirsthighaffinitynon-peptidegastrin-releasingpeptide(BB2)receptorantagonist.BioorgMedChemLett.1998Sep22;8(18):2589-94.[2].SchepetkinIA,etal.Gastrin-releasingpeptide/neuromedinBreceptorantagonistsPD176252,PD168368,andrelatedanalogsarepotentagonistsofhumanformyl-peptidereceptors.MolPharmacol.2011Jan;79(1):77-90.[3].MoodyTW,etal.Nonpeptidegastrinreleasingpeptidereceptorantagonistsinhibittheproliferationoflungcancercells.EurJPharmacol.2003Aug1