PMC:3750932 / 97518-99207
Annnotations
2_test
{"project":"2_test","denotations":[{"id":"23829793-17764960-81675579","span":{"begin":195,"end":198},"obj":"17764960"},{"id":"23829793-17545310-81675580","span":{"begin":410,"end":413},"obj":"17545310"},{"id":"23829793-18552131-81675581","span":{"begin":575,"end":578},"obj":"18552131"},{"id":"23829793-22918043-81675582","span":{"begin":764,"end":767},"obj":"22918043"},{"id":"23829793-18552131-81675583","span":{"begin":984,"end":987},"obj":"18552131"},{"id":"23829793-22362844-81675584","span":{"begin":1173,"end":1176},"obj":"22362844"},{"id":"23829793-22362844-81675585","span":{"begin":1483,"end":1486},"obj":"22362844"},{"id":"T86497","span":{"begin":195,"end":198},"obj":"17764960"},{"id":"T19218","span":{"begin":410,"end":413},"obj":"17545310"},{"id":"T72714","span":{"begin":575,"end":578},"obj":"18552131"},{"id":"T75740","span":{"begin":764,"end":767},"obj":"22918043"},{"id":"T40582","span":{"begin":984,"end":987},"obj":"18552131"},{"id":"T81788","span":{"begin":1173,"end":1176},"obj":"22362844"},{"id":"T43792","span":{"begin":1483,"end":1486},"obj":"22362844"}],"text":"Selexipag \nSelexipag is an orally active prodrug metabolized to the highly selective prostacyclin IP receptor agonist ACT-333679 (previously known as MRE-269), which has a half-life of over 6 h [257]. With in high selectivity for the IP receptor over other prostanoid receptors (at least 130-fold selectivity), selexipag can be distinguished from beraprost or iloprost currently used in the management of PAH [258]. With no affinity for the prostaglandin E receptor 3 (EP3), selexipag exerts similar vasodilatory activity on both large and small pulmonary arterial branches [259] and its relaxant efficacy is not modified under conditions associated with PAH, whereas relaxation to treprostinil may be limited in the presence of mediators of disease such as ET-1 [260]. Preclinical study results showed that twice-daily administration of selexipag attenuates right ventricular hypertrophy, improves pulmonary hemodynamics, and significantly increases survival in MCT-treated PH rats [259].\nA phase II study, involving 43 PAH patients showed that treatment with selexipag for 17 weeks conferred significant improvements in PVR (−30.3% versus placebo) compared with placebo [261]. Treatment with selexipag was well tolerated by most patients in this study. Adverse events were consistent with the known side effect profile of IPr agonism such as headache, pain in extremity, pain in jaw, nausea, and diarrhea. These side effects decreased over time in patients treated with selexipag [261].\nA phase III randomized trial GRIPHON [262] to examine the effect of selexipag on morbidity and mortality in PAH is underway and will afford more information regarding efficacy and safety of selexipag."}
NEUROSES
{"project":"NEUROSES","denotations":[{"id":"T5043","span":{"begin":34,"end":40},"obj":"PATO_0002354"},{"id":"T5044","span":{"begin":41,"end":48},"obj":"CHEBI_50266"},{"id":"T5045","span":{"begin":85,"end":97},"obj":"CHEBI_15552"},{"id":"T5046","span":{"begin":110,"end":117},"obj":"CHEBI_48705"},{"id":"T5047","span":{"begin":209,"end":213},"obj":"PATO_0000469"},{"id":"T5048","span":{"begin":257,"end":267},"obj":"CHEBI_26347"},{"id":"T5049","span":{"begin":360,"end":368},"obj":"CHEBI_63916"},{"id":"T5050","span":{"begin":405,"end":408},"obj":"CHEBI_33848"},{"id":"T5051","span":{"begin":655,"end":658},"obj":"CHEBI_33848"},{"id":"T5052","span":{"begin":1021,"end":1024},"obj":"CHEBI_33848"},{"id":"T5053","span":{"begin":1597,"end":1600},"obj":"CHEBI_33848"},{"id":"T5055","span":{"begin":405,"end":408},"obj":"CHEBI_31204"},{"id":"T5056","span":{"begin":655,"end":658},"obj":"CHEBI_31204"},{"id":"T5057","span":{"begin":1021,"end":1024},"obj":"CHEBI_31204"},{"id":"T5058","span":{"begin":1597,"end":1600},"obj":"CHEBI_31204"},{"id":"T5060","span":{"begin":405,"end":408},"obj":"CHEBI_53305"},{"id":"T5061","span":{"begin":655,"end":658},"obj":"CHEBI_53305"},{"id":"T5062","span":{"begin":1021,"end":1024},"obj":"CHEBI_53305"},{"id":"T5063","span":{"begin":1597,"end":1600},"obj":"CHEBI_53305"},{"id":"T5065","span":{"begin":405,"end":408},"obj":"CHEBI_104011"},{"id":"T5066","span":{"begin":655,"end":658},"obj":"CHEBI_104011"},{"id":"T5067","span":{"begin":1021,"end":1024},"obj":"CHEBI_104011"},{"id":"T5068","span":{"begin":1597,"end":1600},"obj":"CHEBI_104011"},{"id":"T5070","span":{"begin":424,"end":432},"obj":"PATO_0002070"},{"id":"T5071","span":{"begin":441,"end":454},"obj":"CHEBI_26333"},{"id":"T5072","span":{"begin":530,"end":535},"obj":"PATO_0000586"},{"id":"T5073","span":{"begin":540,"end":545},"obj":"PATO_0000587"},{"id":"T5074","span":{"begin":682,"end":694},"obj":"CHEBI_50861"},{"id":"T5075","span":{"begin":702,"end":709},"obj":"PATO_0000392"},{"id":"T5076","span":{"begin":717,"end":725},"obj":"PATO_0000070"},{"id":"T5077","span":{"begin":859,"end":864},"obj":"PATO_0000367"},{"id":"T5078","span":{"begin":877,"end":888},"obj":"PATO_0000584"},{"id":"T5079","span":{"begin":992,"end":997},"obj":"PATO_0000083"},{"id":"T5080","span":{"begin":1491,"end":1496},"obj":"PATO_0000083"},{"id":"T5081","span":{"begin":1275,"end":1285},"obj":"PATO_0000990"},{"id":"T5082","span":{"begin":1324,"end":1327},"obj":"CHEBI_30353"},{"id":"T5083","span":{"begin":1427,"end":1436},"obj":"PATO_0001997"},{"id":"T5084","span":{"begin":1442,"end":1446},"obj":"PATO_0001309"},{"id":"T5085","span":{"begin":1442,"end":1446},"obj":"PATO_0000165"},{"id":"T5086","span":{"begin":1570,"end":1579},"obj":"PATO_0001415"},{"id":"T5179","span":{"begin":859,"end":888},"obj":"PM8091"}],"text":"Selexipag \nSelexipag is an orally active prodrug metabolized to the highly selective prostacyclin IP receptor agonist ACT-333679 (previously known as MRE-269), which has a half-life of over 6 h [257]. With in high selectivity for the IP receptor over other prostanoid receptors (at least 130-fold selectivity), selexipag can be distinguished from beraprost or iloprost currently used in the management of PAH [258]. With no affinity for the prostaglandin E receptor 3 (EP3), selexipag exerts similar vasodilatory activity on both large and small pulmonary arterial branches [259] and its relaxant efficacy is not modified under conditions associated with PAH, whereas relaxation to treprostinil may be limited in the presence of mediators of disease such as ET-1 [260]. Preclinical study results showed that twice-daily administration of selexipag attenuates right ventricular hypertrophy, improves pulmonary hemodynamics, and significantly increases survival in MCT-treated PH rats [259].\nA phase II study, involving 43 PAH patients showed that treatment with selexipag for 17 weeks conferred significant improvements in PVR (−30.3% versus placebo) compared with placebo [261]. Treatment with selexipag was well tolerated by most patients in this study. Adverse events were consistent with the known side effect profile of IPr agonism such as headache, pain in extremity, pain in jaw, nausea, and diarrhea. These side effects decreased over time in patients treated with selexipag [261].\nA phase III randomized trial GRIPHON [262] to examine the effect of selexipag on morbidity and mortality in PAH is underway and will afford more information regarding efficacy and safety of selexipag."}