Yuan-Ping Pang, Principal Investigator

Development of Second-Generation Farnesyltransferase Inhibitors as Cancer Drugs

The high prevalence of mutated Ras genes in human cancers makes Ras protein a suitable target for cancer drug development. One way to block the aberrant Ras functions is to inhibit farnesyltransferase (FTase), which modifies pro-Ras protein with the farnesyl isoprenoid lipid that is required for Ras protein’s biological activities. Such inhibitors do not substantially interfere with normal cell growth, thus providing a promising approach to cancer chemotherapy. Indeed, first-generation farnesyltransferase inhibitors as potential cancer drugs are currently in Phase II clinical trials.

This research group’s objective is to develop second-generation FTase inhibitors supplementing those currently in clinical trials with the aid of high-speed computing. Their specific aim is to identify FTase inhibitor leads by computationally screening chemical databases using an advanced docking program, eudoc, that permits docking studies with metalloproteins and uses “spatial-decomposition” to achieve 100% parallelism. Five million druggable, commercially available compounds will be computationally screened against FTase by conducting a large-scale, high resolution docking study. The computationally identified leads will then be tested experimentally and optimized by using combinatorial chemistry and medicinal chemistry.

Research Group

Min He, Research Associate
Thomas Kollmeyer, Staff
Ganesh Kumar, Research Associate
Isidro Merino, Research Associate
James D. Xidos, Staff