Description
Macitentanisadualendothelinreceptor(ET-A/B)antagoNISTthatdisplaysantihypertensive,anti-fibrotic,andanticanceractivity;thiscompoundexhibitsslowerreceptordissociationkineticsthanotherendothelinreceptorantagonists.Macitentaniscurrentlyusedtotreatpulmonaryarterialhypertension,asclinicaltrialsshowthatitdecreasesbloodpressureandproteinuriaandpreventsrightventriclehypertrophy.Inmodelsofsystemicsclerosis,macitentanslowedthefibroticprocess.Inotheranimalmodels,macitentanenhancedtoxicityofavarietyofotherchemotherapeutics,increasingapoptosisintumorcellsanddecreasinglevelsofphosphorylatedVEGFR2,phosphorylatedAkt,andMAPK.
References
PulidoT,AdzerikhoI,ChannickRN,etal.Macitentanandmorbidityandmortalityinpulmonaryarterialhypertension.NEnglJMed.2013Aug29;369(9):809-18.PMID:23984728.
CoralloC,PecettiG,IglarzM,etal.Macitentanslowsdownthedermalfibroticprocessinsystemicsclerosis:invitrofindings.JBiolRegulHomeostAgents.2013Apr-Jun;27(2):455-62.PMID:23830395.
GatfieldJ,MuellerGrandjeanC,SasseT,etal.Slowreceptordissociationkineticsdifferentiatemacitentanfromotherendothelinreceptorantagonistsinpulmonaryarterialsmoothmusclecells.PLoSOne.2012;7(10):e47662.PMID:23077657.
KimSJ,KimJS,KimSW,etal.Antivasculartherapyformultidrug-resistantovariantumorsbymacitentan,adualendothelinreceptorantagonist.TranslOncol.2012Feb;5(1):39-47.PMID:22348175.
KimSJ,KimJS,KimSW,etal.Macitentan(ACT-064992),atissue-targetingendothelinreceptorantagonist,enhancestherapeuticefficacyofpaclitaxelbymodulatingsurvivalpathwaysinorthotopicmodelsofmetastatichumanovariancancer.Neoplasia.2011Feb;13(2):167-79.PMID:21403842.
IglarzM,BinkertC,MorrisonK,etal.Pharmacologyofmacitentan,anorallyactivetissue-targetingdualendothelinreceptorantagonist.JPharmacolExpTher.2008Dec;327(3):736-45.PMID:18780830.
