OICR-9429-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOICR-9429Cat.No.:HY-16993CASNo.:1801787-56-3分?式:C??H??F?N?O?分?量:555.59作?靶點(diǎn):HistoneMethyltransferase;Apoptosis作?通路:Epigenetics;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥32mg/mL(57.60mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.7999mL8.9994mL17.9989mL5mM0.3600mL1.7999mL3.5998mL10mM0.1800mL0.8999mL1.7999mL請根據(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。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/5MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(4.50mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.50mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.50mM);ClearsolutionBIOLOGICALACTIVITY?物活性O(shè)ICR-9429?種?親和?的WD重復(fù)域5(WDR5)抑制劑，通過結(jié)合WDR5的中?肽結(jié)合袋，競爭性地阻斷WDR5與MLL蛋?的相互作?。OICR-9429可抑制組蛋?H3K4三甲化，可?于?MLL重排??病、結(jié)腸癌、胰腺癌、前列腺癌、膀胱癌(BCa)等多種癌癥的研究。IC50&TargetIC50:67.74μM(T24cell);0.41μM(UM-UC-3cell);121.42μM(TCCSUP)[1]體外研究OICR-9429(0-10μM,48h)showshighsensitivityforT24,UM-UC-3withIC50valuesof67.74μMand70.41μM,respectively[1].OICR-9429(0-10μM,48h)showslowsensitivityforTCCSUPwithIC50valuesof121.42μM[1].OICR-9429(70μM,120μM,140μMand240μM;48h)reducesBCacellviabilitybydecreasingWDR5-mediatedH3K4me3[1].OICR-9429(70μM,120μM,140μMand240μM;48h)inhibitstheproliferationofBCacellsbyregulatingtheG1/Sphasetransition[1].OICR-9429(70μM,120μM,140μMand240μM;24h)enhancesapoptosisofBCacellsinatime-dependentanddose-dependentmannerandpromotescisplatinchemosensitivityinBCacells[1].OICR-9429(70μM,120μM,140μMand240μM;24h,48h)suppressesthemetastaticbehaviourofbladdercancercells[1].OICR-9429(70μM,120μM,140μMand240μM;48h)suppressesPD-L1expressioninducedbyIFN-γinBCacells[1].CellProliferationAssay[1]CellLine:BCacelllines(T24,UM-UC-3andTCCSUP)Concentration:70μM,120μM,140μMand240μMIncubationTime:5daysResult:HadalowproliferationrateandremarkablyreducedthenumberofcoloniesformedbythethreeBCacelllinesinadose-dependentmanner.CellCytotoxicityAssay[1]CellLine:BCacelllines(T24,UM-UC-3andTCCSUP)Concentration:0-10μM2/5MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:48hResult:Inhibitedcellviabilityinadose-dependentmannerinBCacelllines.ApoptosisAnalysis[1]CellLine:BCacelllines(T24,UM-UC-3andTCCSUP)Concentration:70μM,120μM,140μMand240μMIncubationTime:24hResult:Showednoobviousapoptoticcellsfor24hbuttheapoptoticratewassignificantlyincreasedat72handupregulatedcaspase3/7activity.CellMigrationAssay[1]CellLine:BCacelllines(T24,UM-UC-3andTCCSUP)Concentration:70μM,120μM,140μMand240μMIncubationTime:24h,48hResult:ReducedthemigratoryspeedanddecreasedthemigrationofthethreeBCacelllines.CellInvasionAssay[1]CellLine:BCacelllines(T24,UM-UC-3andTCCSUP)Concentration:70μM,120μM,140μMand240μMIncubationTime:24h,48hResult:DecreasedtheinvasionofthethreeBCacelllines.WesternBlotAnalysis[1]CellLine:BCacelllines(T24,UM-UC-3andTCCSUP)Concentration:70μM,120μM,140μMand240μMIncubationTime:48hResult:ShowedsignificantdownregulationofH3K4me3intreatedcellsbutnotWDR5ortotalH3.ReducedtheexpressionofPD-L1inducedbyIFN-γinadose-dependentmanneratboththeRNAandproteinlevels.RT-PCR[1]3/5MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:BCacelllines(T24,UM-UC-3andTCCSUP)Concentration:70μM,120μM,140μMand240μMIncubationTime:48hResult:Downregulatedsomegenesrelatedtothecellcycle,suchasCDK1,PLK1,CCNE2,CCNB1,CCNA2,AURKA,andE2F1,genesrelatedtoapoptosisandDNArepair,suchasBIRC5,XRCC2,AURKA,E2F1,andMCM2,andgenesrelatedtometastasis,suchasAURKAandFOXM1.CellCycleAnalysis[1]CellLine:BCacelllines(T24,UM-UC-3andTCCSUP)Concentration:70μM,120μM,140μMand240μMIncubationTime:48hResult:IncreasedthecellpopulationintheG0/G1phaseofthreeBCacellsandreducedcellpopulationintheSandG2/Mphases.體內(nèi)研究OICR-9429(30mg/kgor60mg/kg,i.p)targetingWDR5notonlysuppressedtumourproliferationandenhancetheefficacyofcisplatinforBCacellsinvivobutalsoreducedthetoxicityandsideeffectsfornormaltissues[1].AnimalModel:xenograftmousemodel[1]Dosage:30mg/kg,60mg/kgAdministration:30mg/kg,60mg/kg,i.p.Result:Suppressedtumourgrowth,smalltumoursandenhancedtumoursensitivity.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2019Aug21;10(1):3761.?JExpClinCancerRes.2022May7;41(1):168.?Oncogene.2021Apr;40(15):2711-2724.?ActaPharmacolSin.2021Apr13.?ResearchSquarePreprint.2022Jan.Seemorecustomervalidationsonwww.MedChemEREFERENCES4/5MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].JingtongZhang,etal.TargetingWDrepeatdomain5enhanceschemosensitivityandinhibitsproliferationandprogrammeddeath-ligand1e