PMID- 32431177 OWN - NLM STAT- MEDLINE DCOM- 20210521 LR - 20240329 IS - 1756-8927 (Electronic) IS - 1756-8919 (Print) IS - 1756-8919 (Linking) VI - 12 IP - 12 DP - 2020 Jun TI - Advances in mammalian target of rapamycin kinase inhibitors: application to devices used in the treatment of coronary artery disease. PG - 1181-1195 LID - 10.4155/fmc-2019-0304 [doi] AB - 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. FAU - Jinnouchi, Hiroyuki AU - Jinnouchi H AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Guo, Liang AU - Guo L AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Sakamoto, Atsushi AU - Sakamoto A AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Sato, Yu AU - Sato Y AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Cornelissen, Anne AU - Cornelissen A AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Kawakami, Rika AU - Kawakami R AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Mori, Masayuki AU - Mori M AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Torii, Sho AU - Torii S AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Kuntz, Salome AU - Kuntz S AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Harari, Emanuel AU - Harari E AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Mori, Hiroyoshi AU - Mori H AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Fuller, Daniela AU - Fuller D AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Gadhoke, Neel AU - Gadhoke N AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Fernandez, Raquel AU - Fernandez R AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Paek, Ka Hyun AU - Paek KH AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Surve, Dipti AU - Surve D AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Romero, Maria AU - Romero M AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Kolodgie, Frank D AU - Kolodgie FD AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Virmani, Renu AU - Virmani R AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. FAU - Finn, Aloke V AU - Finn AV AD - Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA. LA - eng GR - R01 HL141425/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20200520 PL - England TA - Future Med Chem JT - Future medicinal chemistry JID - 101511162 RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Atherosclerosis/drug therapy MH - Coronary Artery Disease/*drug therapy MH - Humans MH - Protein Kinase Inhibitors/chemistry/*pharmacology MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism PMC - PMC7333590 OTO - NOTNLM OT - mTOR OT - torin OT - vascular device COIS- Financial & competing interests disclosure CVPath Institute has received institutional research support from R01 HL141425 Leducq Foundation Grant; 480 Biomedical; 4C Medical; 4Tech; Abbott; Accumedical; Amgen; Biosensors; Boston Scientific; Cardiac Implants; Celonova; Claret Medical; Concept Medical; Cook; CSI; DuNing, Inc.; Edwards Life Sciences; Emboline; Endotronix; Envision Scientific; Lutonix/Bard; Gateway; Lifetech; Limflo; MedAlliance; Medtronic; Mercator; Merill; Microport Medical; Microvention; Mitraalign; Mitra assist; NAMSA; Nanova; Neovasc; NIPRO; Novogate; Occulotech; OrbusNeich Medical; Phenox; Profusa; Protembis; Qool; Recor; Senseonics; Shockwave; Sinomed; Spectranetics; Surmodics; Symic; Vesper; WL Gore; and Xeltis. A Finn has received honoraria from Abbott Vascular; Biosensors; Boston Scientific; Celonova; Cook Medical; CSI; Lutonix Bard; Sinomed; Terumo Corporation; and is a consultant for Amgen; Abbott Vascular; Boston Scientific; Celonova; Cook Medical; Lutonix Bard; and Sinomed. R Virmani has received honoraria from Abbott Vascular; Biosensors; Boston Scientific; Celonova; Cook Medical; Cordis; CSI; Lutonix Bard; Medtronic; OrbusNeich Medical; CeloNova; SINO Medical Technology; ReCore; Terumo Corporation; WL Gore; Spectranetics; and is a consultant for Abbott Vascular; Boston Scientific; Celonova; Cook Medical; Cordis; CSI; Edwards Lifescience; Lutonix Bard; Medtronic; OrbusNeich Medical; ReCore; Sinomededical Technology; Spectranetics; Surmodics; Terumo Corporation; WL Gore; Xeltis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. EDAT- 2020/05/21 06:00 MHDA- 2021/05/22 06:00 PMCR- 2021/03/01 CRDT- 2020/05/21 06:00 PHST- 2020/05/21 06:00 [pubmed] PHST- 2021/05/22 06:00 [medline] PHST- 2020/05/21 06:00 [entrez] PHST- 2021/03/01 00:00 [pmc-release] AID - 10.4155/fmc-2019-0304 [doi] PST - ppublish SO - Future Med Chem. 2020 Jun;12(12):1181-1195. doi: 10.4155/fmc-2019-0304. Epub 2020 May 20.