Results in action
Large pharma, biotech, CROs, and universities rely on MCPairs to design critical compounds and advance drug candidates.
With over 60 years of combined drug discovery experience and 150+ publications and patents, we support clients across all research phases. Our software accelerates project delivery, while our consultancy work continuously drives new features and innovation.
Polypharmacology of multiple GPCR targets
The client’s project was investigating poly-pharmacology effects of a combination of antagonism at two or more Class A GPCRs.
MedChemica examined the data from the literature and patents, performing both matched molecular pair analysis (MMPA), and model building to predict potency, based on random forest of the unique fragments generated by the MMPA. Using the analysis, key groups were identified where potency was gained at the GPCR targets, and critically, where changes could be made. MCPairs Compounds-From-Rules generated ideas, and with further ideas from project medicinal chemists, were tested in-silico with the potency prediction models. Reduction to practice by the synthesis of these molecules generated novel compounds, and actives, to test in-vivo for the desired pharmacology.
The diagram above illustrates the process and plots where key side chains were highlighted.
SOS1 patent landscape
Indole-3-glyoxylamide-Based Series of Tubulin Polymerization Inhibitors
Researches at the University of Sheffield wished to produce quality molecules possessing both in-vitro activity at the primary target and sufficient aqueous solubility and metabolism profile.
A small set of compounds were selected from the output of MCPairs Online RuleDesign where solubility was selected as the goal. Synthesis of these led to compound 59 (see diagram) with sufficient aqueous solubility to formulate, and dose, in a mouse xenograph study and show efficiency.
The results were published in 2015 and further investigations are on-going.
Case Study: Improve Metabolic Stability
Case Study: Project Assessment for Revolution Medicines
For many years, MedChemica has acted as project consultant on the tri-complex ”Molecular Glues” yielding K-RAS(ON) inhibition.
