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Molecular activity of sirolimus and its possible application in tuberous sclerosis treatment
Author(s) -
Jozwiak Jaroslaw,
Jozwiak Sergiusz,
Oldak Monika
Publication year - 2006
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.20049
Subject(s) - sirolimus , tuberous sclerosis , pi3k/akt/mtor pathway , fkbp , cancer research , kinase , medicine , biology , pharmacology , signal transduction , microbiology and biotechnology , pathology
Sirolimus is one of the intensively investigated drugs with pluripotent activities. It binds to its intracellular receptor FKBP12 (FK506‐binding protein 12), a member of the family of FK506‐binding proteins, and inhibits the activity of mTOR, a serine/threonine kinase involved in numerous cell processes linked to cell growth control. The drug is currently registered for the prophylaxis of organ rejection and for use in coronary stents. However, unique characteristics of sirolimus make it a good candidate for anti‐cancer therapy. Indeed, phase II and III clinical studies in humans with several types of neoplasms are already under way. The review describes molecular activity of sirolimus and its analogs, characteristic for specific applications, in view of very recent advances involving tuberous sclerosis complex (TSC)‐mediated signaling pathways. Current studies with sirolimus performed in tuberous sclerosis animal models are presented. Possible application of sirolimus for treating tuberous sclerosis, disease caused by mutations of TSC proteins, is discussed. © 2005 Wiley Periodicals, Inc. Med Res Rev

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