Cheminformatics aided discovery of novel COMT inhibitors for Parkison’s Disease Treatment

Host Organisation: NovaMechanics Ltd
Partner Organisation(s): PA 1: Erevnitko Idryma P. L. PA 2: The Cyprus Ins
Project Budget: 261.697,15 €
IDEK Funding: 199.999,27 €

The project aims at using advanced computational techniques to identify potent and superior compounds used for the treatment of Parkinson’s Ɵtute of Neurology and GeneƟcs disease (PD), a neurological disorder with no cure that affects millions of people with devastating effects on the quality of life of patients. Specifically, the project aims at identifying novel COMT inhibitors, a class of compounds commonly used in the symptomatic treatment of PD, in combination with L-DOPA and carbidopa, and aim to increase the availability of this drug to alleviate the symptoms. Accordingly, the objective of the project is to identify compounds that are potent COMT inhibitors and therefore could be of significant interest for the PD treatment. Towards this end we will develop the necessary computational and experimental methods and tools in order to: (i) identify potent COMT inhibitors among compounds already synthesized and deposited in large databases and (ii) repurpose existing drugs that would also act as COMT inhibitors. To accomplish our goal, computational tools developed within the project will be based on ligand- as well as structure- based techniques and will generate strong evidence on the compounds potency to act as COMT inhibitors. Based on a consensus scheme that will incoorporate both ligandand structure- based methods and more filters that will be applied (including in silico toxicity assessment, Lipinski rule of five, ADME properties assessment and investigating for Pan-Assay Interference Compounds (PAINS) – promiscuous compounds etc), a priority list of potential COMT inhibitors will be proposed. Among those, the top ranked compounds and FDA approved drugs (repurposed drugs) will be sourced and tested in vitro for the ability to inhibit COMT. Ultimately, some compounds that show strong inhibitory action will be identified. The most promising compounds will be tested in vivo and compared to currently marketed drug, entacapone.