Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPD176252Cat.No.:HY-103286CASNo.:204067-01-6分?式:C??H??N?O?分?量:584.67作?靶點(diǎn):BombesinReceptor作?通路:GPCR/GProtein儲(chǔ)存?式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:115mg/mL(196.69mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.7104mL8.5518mL17.1037mL5mM0.3421mL1.7104mL3.4207mL10mM0.1710mL0.8552mL1.7104mL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(storedundernitrogen)。-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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/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:5.75mg/mL(9.83mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥5.75mg/mL(9.83mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性PD176252?種有效的BB1和BB2拮抗劑，能夠抑制?BB1和BB2受體和??BB1和BB2受體活性，Ki值分別為0.17nM，1nM和0.66nM，16nM；PD176252同時(shí)為FPR1/FPR2的激動(dòng)劑，在HL-60細(xì)胞中，EC50值分別為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]體外研究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].體內(nèi)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?邊的抑制劑?師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