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Rapamycin: Something Old, Something New, Sometimes Borrowed and Now Renewed
Author(s) -
Hartford C M,
Ratain M J
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100317
Subject(s) - sirolimus , pi3k/akt/mtor pathway , autophagy , mtorc1 , angiogenesis , pharmacology , biology , cancer research , medicine , signal transduction , microbiology and biotechnology , genetics , apoptosis
The molecular target of rapamycin (mTOR) is central to a complex intracellular signaling pathway and is involved in diverse processes including cell growth and proliferation, angiogenesis, autophagy, and metabolism. Although sirolimus (rapamycin), the oldest inhibitor of mTOR, was discovered more than 30 years ago, renewed interest in this pathway is evident by the numerous rapalogs recently developed. These newer agents borrow from the structure of sirolimus and, although there are some pharmacokinetic differences, they appear to differ little in terms of pharmacodynamic effects and overall tolerability. Given the multitude of potential applications for this class of agents and the decrease in cost that can be expected upon the expiration of sirolimus patents, renewed focus on this agent is warranted. Clinical Pharmacology & Therapeutics (2007) 82 , 381–388. doi: 10.1038/sj.clpt.6100317 ; published online 29 August 2007