Premium
Platforms and networks in triterpenoid pharmacology
Author(s) -
Sporn Michael B.,
Liby Karen,
Yore Mark M.,
Suh Nanjoo,
Albini Adriana,
Honda Tadashi,
Sundararajan Chitra,
Gribble Gordon W.
Publication year - 2007
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20179
Subject(s) - oleanolic acid , betulinic acid , triterpenoid , ursolic acid , oleanane , chemistry , pharmacology , terpene , computational biology , biochemistry , biology , stereochemistry , medicine , triterpene , genetics , alternative medicine , pathology , chromatography
Abstract Using the pentacyclic, naturally occurring triterpenoids, oleanolic, ursolic, and betulinic acids, as starting materials, we have developed a new series of multifunctional drugs for potential clinical use. These agents have anti‐inflammatory, anti‐oxidative, anti‐proliferative, pro‐apoptotic, and differentiating activities. Two synthetic oleanane triterpenoids, 2‐cyano‐3,12‐dioxooleana‐1,9(11)‐dien‐28‐oic acid (CDDO) and its C‐28 methyl ester (CDDO‐Me), are presently in Phase I clinical trials in cancer patients. Three themes are emphasized in this review: (1) The importance of the unique structures of the triterpenoid platforms that have been used as a start for new synthesis; (2) The concept that these new drugs interact with entire physiological networks, rather than solely with single molecular targets; and (3) The coupling in real time between the triterpenoid platforms and the physiological networks with which they interact, as seen in the reversibility of the Michael reactions, which mediate their activity. We suggest that further development of such new, multifunctional drugs will most likely occur in the more flexible environment of small biotech or pharmaceutical companies. Drug Dev Res 68:174–182, 2007. © 2007 Wiley‐Liss, Inc.