Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPDE4-IN-12Cat.No.:HY-151174分?式:C??H??NO?分?量:553.64作?靶點(diǎn):Phosphodiesterase(PDE)作?通路:MetabolicEnzyme/Protease儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PDE4-IN-12?種強(qiáng)效的PDE4泛型抑制劑，其對(duì)PDE4和PDE7的IC50值分別為3.5和15nM(SI分別為2.71和4.27)。PDE4-IN-12具有較好的安全性，可?于炎癥性腸病(IBDs)的研究。IC50&TargetPDE4D2PDE4B2PDE5A1PDE7A3.51nM(IC50)9.51nM(IC50)1.24μM(IC50)15nM(IC50)PDE10APDE8A11.02μM(IC50)194nM(IC50)體外研究PDE4-IN-12(compound22d)(10,20μM;24h)reducesthereleaseofNOinLPSinducedinflammationcellmodel(indicatesanti-inflammatoryeffect)[1].CellViabilityAssay[1]CellLine:Raw264.6cellsConcentration:10,20μMIncubationTime:24hResult:ReducedtheNOreleasebydose-dependentmannerintheLPSinducedinflammatorycellmodel.體內(nèi)研究PDE4-IN-12(5mg/kg;i.p.;twicedailyfor8days)amelioratesmouseacutecolitisinducedbyDSS(dextransulfatesodium)[1].1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEPDE4-IN-12(10mg/kg;p.o.;single)showswelltoleratedindogs[1].PDE4-IN-1(2.5mg/kg;i.v.;single)showsgreatplasmaexposure,withT1/2andAUC0-24hvaluesof4.18hand6522hng/mL[1].AnimalModel:MaleC57BL/6mice(5to6-weekold;15-17g;DSS-inducedmousemodel)[1].Dosage:5mg/kgAdministration:Intraperitonealinjection;twicedailyfor8days.Result:Amelioratedtheacutecolitisbydecreasingdiseaseactivityindex,increasingthecolonlength,andalsoamelioratingthepathologicaldamages.AnimalModel:Beagledogs[1].Dosage:10mg/kg(solvedin0.5%CMC-Nasolution).Administration:Oraladministration;single.Result:Exhibitedgoodsafety,whichcausednoemesisonbeagledogsat10mg/kg.AnimalModel:MaleC57BL/6mice(5to6-weekold;15-17g)[1].

Dosage:2.5mg/kgAdministration:Intravenousinjection;single.Result:1.19PharmacokineticParametersofPDE4-IN-12inMaleC57BL/6mice[1].T1/2(h)AUC0-24h(h?ng/mL)MRT0-24h(h)CL(mL/min/kg)Vss(mL/kg)IV(2.5mg/kg)4.1865221.766.40673REFERENCES[1].LiuH,etal.DiscoveryofnovelPDE4inhibitorstargetingtheM-pocketfromnaturalmangostaninwithimprovedsafetyforthetreatmentofInflammatoryBowelDiseases.EurJMedChem.2022Aug9;242:114631.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresear