Simulations Plus Announces Success in COX-2/COX-1 Drug Design Project
Simulations Plus, Inc. (NASDAQ: SLP), a leading provider of consulting services and software for pharmaceutical discovery and development, today announced that its second NCE (new chemical entity) initiative, which involved using Simulations Plus software to design molecules to inhibit COX-2, has been a success as determined by synthesis and testing by a third-party lab. Three of the four molecules it has designed are potent inhibitors of both cyclooxygenase-2 (COX-2) and COX-1 enzymes. The fourth inhibits COX-2 but only weakly inhibits COX-1.
Dr. Robert Clark, director of cheminformatics sciences for Simulations Plus, said: “We’re very pleased to report that our second NCE project has again demonstrated that our ADMET Design Suite™ (ADMET Predictor™, MedChem Studio™, and MedChem Designer™, supplemented by GastroPlus™ simulations) provides tools that can rapidly and inexpensively generate new lead molecules with affinity for selected targets. This project was more challenging than the malaria NCE project we completed two years ago because this time our goal was to inhibit two targets with a single molecule while also providing good ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties. Southern Research Institute in Birmingham, Alabama, performed the chemical synthesis and Cerep in Redmond, Washington, performed the COX-2 and COX-1 assays.”
Dr. Michael Lawless, team leader for cheminformatics studies at Simulations Plus, added: “The only COX-2 inhibitor remaining on the U.S. market is Celebrex® (celecoxib), after Vioxx® (rofecoxib) and others were withdrawn for cardiotoxicity side effects. Research after the Vioxx withdrawal indicated that to avoid cardiotoxicity when inhibiting COX-2, it is important to also inhibit COX-1 but to a lesser extent. Needless to say, we’re delighted that we were able to hit two targets with three of four molecules, and one of them is potent as well as having the desired property of higher affinity for COX-2 than for COX-1. The fact that these molecules were designed using only our own software suite is a testament to the capabilities provided by these powerful programs.”
Walt Woltosz, chairman and chief executive officer of Simulations Plus, added: “Once again we stuck our necks out and announced prior to synthesis that we were going to contract with a company to synthesize several molecules of our own design and have them tested to see if we were successful. In just a few months, and for a mere fraction of the normal cost required to design new lead molecules to hit one target, we were able to design single molecules that each hit two different targets. This process might take years using traditional methodologies. We are not aware of any other software company that has applied its tools in this way – to take the risk of designing new molecules, having them made, then having them tested, while openly announcing ahead of time and providing results as soon as they were available. There is a chance, although it is probably remote, that we might be able to license one or more of these molecules to a company that could take them forward into further structural refinements and development. However, our goal is not to become a drug company, but to show that our software tools provide very powerful capabilities that can dramatically reduce the time and cost to generate good lead molecules for a wide variety of targets. We plan to present our results at upcoming scientific meetings, to customers at on-site visits, and ultimately, to submit a publication to one of the peer-reviewed scientific journals that cover this area of science.”