ACADEMIA

Metabasis Therapeutics, a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs for the treatment of metabolic and liver diseases by targeting the liver and liver pathways, announced today that an article entitled “Relative Binding Affinities of Fructose-1,6-Bisphosphatase Inhibitors Calculated Using a Quantum Mechanics-Based Free Energy Perturbation Method” by M. Rami Reddy and Mark Erion, was published in the Journal of the American Chemical Society (JACS), Vol. 129, Issue No. 30, pp. 9296-9297, (2007). The publication describes the integration of Quantum Mechanics (QM) into a method known as free energy perturbation (FEP) and the use of the resulting QM/molecular mechanics (MM)-based FEP method for drug design. The communication also included a novel computer-aided drug design strategy for achieving accurate predictions that has been used by Metabasis to calculate the relative inhibitory potencies of several structurally-diverse fructose-1,6-bisphosphatase (FBPase) inhibitors. This method has been used by Metabasis in its drug discovery programs focused on the use of these inhibitors for the treatment of type 2 diabetes. The results were shown to be consistent with experimental data thereby demonstrating both the accuracy of the method and its potential in drug design. “The publication of this communication in JACS reflects the potential value of the QM/MM-based FEP approach in drug discovery,” stated Dr. Mark Erion, Metabasis’ executive vice president of research and development and chief scientific officer. “The use of this method can provide important insights into the binding interactions of drug candidates and thereby enable better selection of candidate compounds to be synthesized and tested. In addition, unlike conventional FEP approaches, the QM/MM-based method is capable of automation and code parallelization which will increase throughput and ultimately significantly reduce the time and cost to discover potential drug candidates.” For the past 4 years, Dr. Reddy, senior director of computational chemistry, structural biology and cheminformatics and Dr. Mark Erion, in consultation with Dr. U. Chandra Singh, president and chief scientific officer of AM Technology, have been developing this computational strategy. The calculations reported in the manuscript were conducted on IBM System P570 and P650 multi-processor servers. “Metabasis is applying the same computer-aided design technology used by engineers and industrial designers to automate key parts of the drug-discovery process,” said David Turek, vice president of deep computing at IBM. “The CADD technology running on Metabasis’ IBM System supercomputer significantly reduces the time required for drug-simulation processes by eliminating the need to synthesize and test many of the compounds that would normally be a part of the drug-discovery process.” “Metabasis’ proprietary technology and know-how, including our expertise with computer-aided drug design, has enabled our discovery team to move five product candidates into clinical development since the Company’s inception,” said Dr. Paul Laikind, Metabasis’ president and chief executive officer. “This excellent productivity is continuing with several more metabolic disease candidates discovered by our team approaching a recommendation for further development.”