Recent advances in the chemistry, biosynthesis and pharmacology of rapamycin analogs.
Covering: 2003 to 2008. In the period 1998 to 2003, a number of reviews have appeared evaluating the potential of rapamycin and other immunophilin ligands as therapies for cancer, organ transplantation, restenosis prevention, autoimmune disorders, and neurodegenerative diseases. This review aims to evaluate advances in the field since that time, specifically detailing progress in: (i) the role of rapamycin in inhibiting its principal cellular target, the mammalian target of rapamycin (mTOR) in both of its protein complexes, (ii) understanding the role of specific genes in the mechanism of rapamycin biosynthesis, (iii) the production of novel analogs of rapamycin via precursor-directed biosynthesis, (iv) the enzymology of the pipecolate incorporating enzyme (RapL) in vitro, and (v) the pharmacology and mechanistic chemical biology of rapamycin analog mediated neuroprotection and neuroregeneration.
Graziani
Edmund I
EI
Department of Chemical Sciences, Wyeth Research, 401 N. Middletown Rd, Pearl River, NY 10965, USA.
D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D020123:Sirolimus / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases
D007166:Immunosuppressive Agents; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus