THR-123-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemETHR-123Cat.No.:HY-P11354分子式: C₈₃H₁₂₄N₂₂O₂₇S₂分子量: 1926.13Sequence: Cys-Tyr-Phe-Asp-Asp-Ser-Ser-Asn-Val-Leu-Cys-Lys-Lys-Tyr-Arg-Ser(disulfidebridge:Cys1-Cys11)SequenceShortening:CYFDDSSNVLCKKYRS(disulfidebridge:Cys1-Cys11)作用靶点: TGF-βReceptor;Apoptosis;InterleukinRelated;Integrin;Cadherin作用通路: TGF-beta/Smad;Apoptosis;Immunology/Inflammation;Cytoskeleton储存方式: PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性THR-123是一种口服有效的ALK3多肽激动剂。THR-123与ALK2的结合相对较弱，但不与ALK6结合。THR-123可抑制炎症、细胞凋亡(apoptosis)和上皮间质转化，并逆转五种急性和慢性肾损伤小鼠模型中已形成的纤维化。THR-123可用于研究肾脏纤维化[1]。IC50&TargetBMPR1AIL-6IL-8体外研究THR-123(0-100μM,60min)inhibitstheexpressionofIL-6,IL-8andICAM-1inducedbyTNF-αinaconcentration-dependentmannerinHK-2cells[1].THR-123(250μM)significantlyinhibitsTGF-β1,hypoxia,orcisplatin-inducedcellapoptosisinHK-2cells[1].THR-123(10μM)restorestheexpressionofE-cadherininhibitedbyTGF-β1,reducestheexpressionsofCTGFandSnail1,andreversesthetransformationofcellmorphologyintothemesenchymalform[1].体内研究THR-123(5mg/kg,p.o.,oncedailyfor3weeks)reversesrenalfibrosisinmicewithnephrotoxicserum-inducedchronickidneyfibrosis(NTN)[1].THR-123(5mg/kg,p.o.,oncedailyfor7days)significantlyreducesrenaltubularnecrosisandtissuedamageinischemicre-perfusioninjury(IRI)modelinmice[1].THR-123(5-15mg/kg,p.o.ori.p.,oncedailyfor5-7days)inhibitsinterstitialvolumeexpansionandcollagendepositioninunilateralureteralobstruction(UUO)modelinmice[1].THR-123(5mg/kg,p.o.,oncedailyfrom8weeksto16weeksofage)doesnotaltertheglomerularabnormalities,andsignificantlyinhibitsthetubularatrophyandinterstitialfibrosisseeninCOL4A3KOmice1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemE[1].THR-123(5mg/kg,p.o.,oncedailyfor3months)inhibitstheprogressionoffibrosisassociatedwithadvanceddiabeticnephropathyinmice[1].AnimalModel:Nephrotoxicserumnephritis,NTNmodelestablishedinCD1mice[1]Dosage:5mg/kgAdministration:Oraladministration(p.o.),oncedailyfor3weeksResult:Significantlyreversedthealreadyformedrenalfibrosis,andimproveglomerularsclerosis,renaltubularatrophyandinterstitialfibrosis.Significantlyreducedrenalfunctionindicators.Inhibitedepithelial-mesenchymaltransition(EMT)andreducethenumberofE-cadherinandFSP1double-positiverenaltubularcells.ReducedmacrophageinfiltrationandactivatetheBMP-Smadsignalingpathway(p-Smad1/5).AnimalModel:IRImodelestablishedinC57Bl/6mice(8weeks)[1]Dosage:5mg/kgAdministration:Oraladministration(p.o.),oncedailyfor7daysResult:Significantlyreducedtheproportionofrenaltubularnecrosisandloweredthebloodureanitrogenlevel.Reducedmacrophageinfiltrationandalleviatedcellapoptosis.AnimalModel:UUOmodelestablishedinCD1mice(8-12week)[1]Dosage:5and15mg/kg(p.o.)or5mg/kg(i.p.)Administration:Oraladministration(p.o.)orintraperitonealinjection(i.p.),oncedailyfor5-7daysResult:Inhibitedinterstitialvolumeexpansionandcollagendeposition.Reducedtheexpressionoffibrosismarkers(fibronectinandtypeIcollagen).AnimalModel:Alportsyndromemodelestablishedineightweeks-oldCOL4A3KOmiceonC57Bl/6background[1]Dosage:5mg/kgAdministration:Oraladministration(p.o.),oncedailyfrom8weeksofageto16weeksofageResult:Improvedglomerularsclerosis,tubulardamageandinterstitialfibrosis.RestoredtheexpressionofE-cadherinandreducethefibroblastmarkerFSP1.2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEAnimalModel:Streptozotocin(HY-13753)inducedDiabeticnephropathy,DNmodelestablishedinmaleCD1mice(8week)[1]Dosage:5mg/kgAdministration:Oraladministration(p.o.),oncedailyfor3monthsResult:Reducedmesangialmatrixexpansion,macrophageinfiltrationandcellapoptosis.DelayedthedeteriorationofrenalfunctionincombinationofCaptopril(HY-B0368).REFERENCES[1].SugimotoH,etal.Activin-likekinase3isimportantforkidneyregenerationandreversaloffibrosis.NatMed.2012Feb5;18(3):396-