Open AccessAdvances in mammalian target of rapamycin kinase inhibitors: application to devices used in the treatment of coronary artery disease
Author(s) -
Hiroyuki Jinnouchi,
Liang Guo,
Atsushi Sakamoto,
Yu Sato,
Anne Cornelissen,
Rika Kawakami,
Masayuki Mori,
Sho Torii,
Salomé Kuntz,
Emanuel Harari,
Hiromu Mori,
Daniela Fuller,
Neel Gadhoke,
Raquel Fernandez,
Ka Hyun Paek,
Dipti Surve,
Maria Romero,
Frank D. Kolodgie,
Renu Virmani,
Aloke V. Finn
Publication year - 2020
Publication title -
future medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.708
H-Index - 69
eISSN - 1756-8927
pISSN - 1756-8919
DOI - 10.4155/fmc-2019-0304
Subject(s) - pi3k/akt/mtor pathway , restenosis , neointima , medicine , vascular smooth muscle , sirolimus , coronary artery disease , kinase , pharmacology , cardiology , cancer research , stent , smooth muscle , signal transduction , biology , microbiology and biotechnology
Mammalian target of rapamycin (mTOR) inhibitors have been applied to vascular coronary devices to avoid neointimal growth and have become the predominant pharmacological agents used to prevent restenosis. mTOR inhibitors can affect not only proliferating vascular smooth muscle cells but also endothelial cells and therefore can result in delayed healing of the vessel including endothelialization. Emerging evidence suggests accelerated atherosclerosis due to the downstream negative effects on endothelial barrier functional recovery. The development of neoatherosclerosis within the neointima of drug-eluting stents can result in late thrombotic events. This type of problematic healing response may open the way for specific mTOR kinase inhibitors, such as ATP-competitive mTOR inhibitors. These inhibitors demonstrate a better healing profile than traditional limus-based drug-eluting stent and their clinical efficacy remains unknown.