Simulations Plus Announces Further Success in Malaria Drug Design Project
Simulations Plus, Inc. (NASDAQ: SLP –News ), a leading provider of consulting services and software for pharmaceutical discovery and development, today announced that further testing shows that the newest molecule the Company has designed to inhibit the malaria parasite is nearly three times more potent as an inhibitor of the drug-sensitive 3D7 strain of the malaria parasite than its best previous molecule. In addition, this newest molecule shows nanomolar activity against three drug-resistant strains of the malaria parasite. The term nanomolar activity refers to a concentration expressed in billionths of a mole per liter of fluid needed to inhibit 50% (“IC50”) of the parasites in a laboratory experiment. Typical drug IC50s run from millimolar (1/1000 of a mole per liter of fluid) for less potent drugs to less than 1 nanomolar for extremely potent drugs. The smaller the IC50, the smaller the amount of drug needed to have a therapeutic effect.
Dr. Robert Clark, director of life sciences for Simulations Plus, said: “The results we reported on March 15 showed that of our first five compounds, activity against the drug-sensitive 3D7 strain of the Plasmodium falciparum malaria parasite was seen in all compounds, with one especially active compound at about a 60 nanomolar level. Further testing of the compounds against the drug-resistant strain has now shown that these molecules have activity against that strain as well, although not as potent as for three drug-sensitive strains (about 214 to 467 nanomolar). We have now received one more compound out of synthesis and it is more potent against both the drug-sensitive strain (about 24 nanomolar) and is similar in activity against the three drug-resistant strains (245 to 492 nanomolar). As I noted in March, however, activity alone does not make a drug, and we consider these compounds only lead compounds that will require further development to become drugs. One of the issues with these compounds is that they are rapidly metabolized in human liver microsomes, which means that their molecular structures may be modified too quickly to be useful as they are. Modifying the design of these structures to reduce the metabolic rate is one of the activities often involved in taking lead compounds further into development.”
Walt Woltosz, chairman and chief executive officer of Simulations Plus, added: “We are encouraged that we have been able to use our in silico design tools to design new compounds that are active against an important target the first time out. As I’ve stated before, we began this effort not to design actual drugs, but to demonstrate that our software tools could be used to generate good lead compounds in a small fraction of the time and cost typically required to reach this stage. However, having now achieved that goal, we’re encouraged to press on with some additional testing on these compounds to identify which enzymes are causing the rapid metabolism so we can consider structural changes to lower the metabolic rate. And we’re still waiting for two more compounds to come out of synthesis that we predict will be more potent against the malaria parasite.”