Simulations Plus Completes Molecule Design Phase, Issues RFQs for Molecule Synthesis

Division: PBPK

Simulations Plus, Inc. (NASDAQ: SLP), a leading provider of consulting services and software for pharmaceutical discovery and development, today announced that it has completed the molecule design phase of its malaria NCE (new chemical entity) project, and has issued requests for quotes to synthesize up to twelve compounds for testing.

The NCE project has involved:

  • Beginning with data generously placed into the public domain by GlaxoSmithKline (GSK) for a large number of molecules that had been synthesized and tested against the Plasmodium falciparum (“P. falciparum”) parasite (malaria).
  • Using our MedChem Studio™ software to analyze the molecular structures in the GSK dataset by clustering molecules into classes with similar common substructures (scaffolds).
  • Analyzing the molecules within various classes with respect to their activity against the parasite, as well as their predicted properties for solubility, permeability, metabolism, and various potential toxicities.
  • Building new predictive models for affinity against the parasite using the ADMET Modeler™ module within ADMET Predictor™.
  • Generating many thousands of new molecular structures using the de novo molecule design capabilities in MedChem Studio and MedChem Designer™.
  • Screening the thousands of new molecules with ADMET Predictor to eliminate those with unacceptable ADMET Risk™ (ADMET = Absorption, Distribution, Metabolism, Excretion and Toxicity).
  • Selecting the 12 most interesting molecules for analysis with our GastroPlus™ software to estimate the dosing regimen needed for each of them, considering not only affinity to the target but all relevant ADMET properties that affect oral absorption, metabolism, and plasma concentration-time histories.
  • Preparing a request for quote for chemical synthesis companies and contract research organizations (CROs) to make the 12 compounds and to run a small battery of tests to confirm our predictions.

Dr. Robert Clark, director of life sciences for Simulations Plus, said, “After carefully examining various potential targets for our first new chemical entity design project, we selected malaria as our focus. The generosity of GSK in placing into the public domain a significant database of molecular structures tested against the parasite, along with their experimental data, enabled us to use our tools to build predictive models of molecular activity against the Plasmodium falciparum parasite. Combining our MedChem Studio, MedChem Designer, ADMET Predictor, and GastroPlus software tools for various aspects of the design and analysis enabled us to home in on 12 promising lead candidates much faster and far more economically than traditional design methods would have allowed.”

Walt Woltosz, chairman and chief executive officer of Simulations Plus, added: “Malaria is a devastating disease. According to the World Health Organization, about 3.3 billion people (half the world’s population) are at risk of malaria, resulting in about 250 million cases and one million deaths every year. Every 30 seconds, a child dies of malaria. It is for this reason that the Bill and Melinda Gates Foundation selected malaria as one of its major initiatives. This is an exciting new project, and now we’re to the point of actually making new molecules that, as far as we know, have not existed before and are therefore potentially patentable. It’s a long shot, of course, that we’ll actually come up with a cost-effective cure for malaria, but all new drug developments begin by designing new molecules and testing them. Our primary purpose is to demonstrate that with our suite of software and an initial dataset of molecules tested against a target, scientists can rapidly generate new molecular structures that are expected to not only hit the target, but also to have acceptable ADMET properties. If even one of our 12 molecules performs reasonably well, we will have achieved a major accomplishment in demonstrating in silico drug design using our tools.”