(From left to right: Mark Yore, Megan Padgett, Charlotte Williams, Darlene Royce, Karen Liby, Renee Risingsong, and Michael Sporn)

The Sporn Laboratory has an integrated program at the lab bench that goes all the way from studies on the molecular mechanism of action of chemopreventive drugs to the actual testing of these agents for prevention of cancer and other chronic diseases in experimental animals. New drugs that are being evaluated include not only the synthetic triterpenoids made in the Department of Chemistry at Dartmouth, but also selective estrogen receptor modulators (SERMs) and rexinoids (new agents that are selective for binding to the retinoid X receptors [RXRs]). The Sporn Laboratory is also involved in a number of active scientific collaborations with other laboratories throughout the country. These include studies with Paul Talalay and Thomas Kensler at Johns Hopkins, with John Letterio at Case Western Reserve, with Powel Brown at Baylor, with Carl Nathan and Flint Beal at Cornell, with John Reed at the Burnham Institute, with Lalage Wakefield at the National Cancer Institute, and with Donald Kufe and Keith Blackwell at Harvard. Two of the synthetic triterpenoids that were made for the first time at Dartmouth are now in Phase I clinical trials.

CDDO is 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid. It was first synthesized by Tadashi Honda in Gordon Gribble's lab in the Department of Chemistry at Dartmouth (11 steps from the starting material, the naturally occurring triterpenoid, oleanolic acid). Dozens of analogs of CDDO have since been synthesized to improve its potency or pharmacokinetics. Molecular studies indicate that it interacts with cysteine residues on target proteins by Michael addition. CDDO has anti-inflammatory, anti-proliferative, pro-apoptotic and cytoprotective actions. CDDO and its methyl ester are presently in Phase I clinical trials for treatment of leukemia and solid tumors.