Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEFluacrypyrimCat.No.:HY-W414644CASNo.:229977-93-9分子式:C??H??F?N?O?分子量:426.39作用靶點(diǎn):Parasite;STAT;Phosphatase;MDM-2/p53;Apoptosis作用通路:Anti-infection;JAK/STATSignaling;StemCell/Wnt;MetabolicEnzyme/Protease;Apoptosis儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Fluacrypyrim是一種酯類殺螨劑，同時(shí)也可作為STAT3抑制劑。Fluacrypyrim顯著提高蛋白質(zhì)酪氨酸磷酸酶(PTPs)的活性。Fluacrypyrim通過引發(fā)顯著的G1期阻滯，并顯著降低cyclinD1蛋白和mRNA水平，從而抑制白血病細(xì)胞生長。Fluacrypyrim能夠選擇性抑制STAT3信號(hào)通路，在STAT3依賴性癌細(xì)胞中誘導(dǎo)生長阻滯和細(xì)胞凋亡(apoptosis)。Fluacrypyrim主要通過阻止造血干細(xì)胞(HSCs)凋亡來減輕輻射誘導(dǎo)的造血系統(tǒng)損傷。Fluacrypyrim通過抑制子宮平滑肌收縮和炎癥反應(yīng)，顯示出顯著的鎮(zhèn)痛和抗炎作用[1][2][3][4]。體外研究Fluacrypyrim(FAPM)(3-12h)reducestheapoptosisrateofBMNCsanditssubsets(Lin,Linc-Kit,LK,andLSKcells)afterthe6.5Gyirradiation[1].Fluacrypyrim(5μM,4-10h)decreasescellapoptosisbyregulatingthep53-PUMApathwayintheBMNCcells[1].Fluacrypyrim(0.1-12μM,0-72h)showsastrongconcentration-dependentandtime-dependentinhibitionofHL-60cellsgrowth,withanIC50of3.8μM[2].Fluacrypyrim(1.5-12μM,6-36h)inducesG1arrestofHL-60cellswithdownregulationofcyclin-D1[2].Fluacrypyrim(0.75-12μM,6-36h)significantlyinhibitsconstitutivephosphotyrosinelevelsofSTAT3(tyr705)inHL-60cells,aneffectthatcanbereversedbysodiumpervanadatetreatment[2].Fluacrypyrim(0.75-12μM,12h)inducesadose-dependentincreaseoftyrosinephosphataseactivityinHL-60cells[2].Fluacrypyrim(3-12μM,8-24h)significantlyinhibitsSTAT3-dependentluciferaseactivityinbothIL-6-stimulatedHepG-2cellsandc-Src-transfectedNIH3T3cells[2].Fluacrypyrim(0.75-12μM,24h)suppressesconstitutivelyactiveSTAT3,therebyblockingcyclinD1andc-MycexpressioninHL-60cells[2].Fluacrypyrim(0.75-12μM,24h)preferentiallysuppressesgrowthofcancercellsharboringconstitutively1/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEactiveSTAT3,withIC50sof3.8μM(HL-60cells),6.0μM(K562cells),8.2μM(XG-7cells)and12.3μM(Jurkat-Tcells)[2].Fluacrypyrim(6-24μM,24h)inducescaspase-dependentapoptosisinbreastcarcinomacells(MDA-MB-231cells)thatharborconstitutivelyactivatedSTAT3[2].Fluacrypyrim(0.62-10μM,60min)significantlyinhibitsuterinecontractionsinducedbyDinoprost(PGF2α)(HY-12956),Oxytocin(HY-17571),acetylcholine(Ach)andKClinadose-dependentmanner(pD2valuesrangingfrom5.72to5.92)[3].Fluacrypyrim(2.5-10μM)inhibitsPGF2α-inducedMLC20phosphorylation[3].CellCycleAnalysis[2]CellLine:HL-60cellsandMDA-MB-231cellsConcentration:0,0.75,1.5,3,6,12μMIncubationTime:6,12,24,36hResult:InducedG1arrestinHL-60cellsandMDA-MB-231cells(24μM,48h)RealTimeqPCR[1]CellLine:BMNCcellsConcentration:5μMIncubationTime:10hResult:DownregulatedtheexpressionlevelsofPuma,Bax,andNoxamarkedly.WesternBlotAnalysis[1]CellLine:BMNCcellsConcentration:5μMIncubationTime:4hResult:Downregulatedtheexpressionlevelofproteinofp-p53,p53,Puma,Bax,Noxa,andcleavedCaspase-3.WesternBlotAnalysis[2]CellLine:HL-60,K562andXG-7cellsConcentration:0,0.75,1.5,3,6,12μMIncubationTime:6,12,24,36hResult:DecreasedthelevelofpRb(ser807/881)inHL-60cells(3,6,12μM).ReducedtheexpressionofcyclinD3andCDK4slightlyandsignificantlyonlyinthe2/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEhigherconcentrationsinHL-60cells(3,6,12μM).DecreasedthecyclinD1expressiondose-dependentlyinHL-60cells(3,6,12μM).DecreasedtheSTAT3tyr705phosphorylationwithoutaffectingSTAT3ser727phosphorylationandtotalSTAT3proteinlevelinHL-60,K562andXG-7cells(0,0.75,1.5,3,6,12μM).ReducedtheexpressionofSTAT5onlyatthehighestconcentrationandshowednoalterationonSTAT1inHL-60cells(0,0.75,1.5,3,6,12μM).體內(nèi)研究Fluacrypyrim(20-75mg/kg,i.p.,3-48hbeforeirradiation,singledose)mitigatesIR-inducedhematopoieticsysteminjuryintheC57BL/6J(CD45.2)miceandB6.SJL/BoyJ(CD45.1)mice[1].Fluacrypyrim(50-200mg/kg,i.p.,1hbeforeacidinjection,singledose)reducesAceticacid(HY-Y0319)-inducedwrithingresponseinmice[3].Fluacrypyrim(100-200mg/kg,i.p.,1hbeforePGF2αinjection,singledose)reducesinflammatoryactivitiesandpainresponseonmouseandratswellingmodels[3].AnimalModel:ThemaleC57BL/6J(CD45.2)miceandmaleB6.SJL/BoyJ(CD45.1)mice(6-8weeks)weresubjectedtoeitherasublethaldose(6.5Gy)orlethaldose(8.0,8.5,9.0Gy)oftotalbodyirradiation(TBI)usinga60Coγ-raysourceatadoserateofapproximately62cGy/min[1]Dosage:20,50,75mg/kgAdministration:3,24,and48hbeforeirradiationResult:Amelioratedpancytopeniainthemicesubjectedtoirradiation(20,50,75mg/kg)(6.5Gy).Improvedthesurvivalrateofmiceafterlethalirradiation(50mg/kg)(8.0Gy,8.5Gy,9.0Gy).Alleviatedirradiation-inducedinjurytoBM(6.5Gy).AcceleratedtherecoveryofHSPCsafterirradiationexposure(6.5Gy).Enhancedtheself-renewalcapacityofHSCsafterirradiation(CD45.2:6.5Gy)(CD45.1:9.0Gy)AnimalModel:KMmaleandfemalemice(22-28g)[3]Dosage:50,100,200mg/kgAdministration:i.p.,1hbeforeacidinjectionResult:Reducedaceticacid-inducedwrithingresponseinmiceAnimalModel:KMmaleandfemalemice(22-28g)andfemaleSpragueDawley(SD)rats(120-140g)[3]3/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEDosage:50,100,200mg/kgAdministration:i.p.,1hbeforePGF2αinjectionResult:Reducedinflammatoryactivitiesonmouseandratswellingmodels.ReducedPGF2α-inducedpainresponse.REFERENCESZhangX,etal.FluacrypyrimProtectsHematopoieticStemandProgenitorCellsagainstIrradiationviaApoptosisPrevention.Molecules.2024Feb9;29(4):816.YuZY,etal.Fluacrypyrim,a