Domain Therapeutics and Ono Pharmaceutical inked a collaboration agreement focused on the discovery of small molecule therapeutics targeting GPCRs selected by Ono. Through the partnership Domain will use its DTect-All™ GPCR drug discovery platform and medicinal chemistry and pharmacology expertise to design and optimize small molecule candidates.

Ono retains exclusive global rights to develop and commercialize relevant products, and Domain will receive an up-front fee, research funding, success-based milestones, and future sales royalties. “This collaboration with Ono further confirms the value of our differentiated drug discovery process and of our expertise in the field of GPCRs,” comments Pascal Neuville, Domain’s CEO. “It constitutes an important step toward the objective of Domain Therapeutics to collaborate with pharma partners on integrated projects, from target to drug discovery.”

France-based Domain is dedicated to the discovery and early development of small molecules targeting GPCRs. The firm’s DTect-All platform has been developed to enable the identification of drug candidates acting on all three classes of GPCRs, including those that are generally considered intractable, such as orphan and peptidic receptors. The technology involves establishing a FRET binding assay between the targeted receptor fused to GFP and a fluorescent ligand selected from Domain’s library of GPCR frequent hitter probes. The assay can then be used to screen a library of druggable compounds to identify molecules that can displace the fluorescent ligand or modify receptor conformation.

Domain says this approach can selectively identify positive and negative allosteric modulators, is ideally suited to the discovery of candidates against orphan GPCRs (as a known ligand of the receptor isn’t required), and can also identify silent allosteric modulators, a class of ligand that binds to the receptor but doesn’t display functional activity in a functional assay.

Domain’s internal research/preclinical-stage pipeline includes compounds targeting GPCRs involved in Parkinson’s disease, Alzheimer’s disease, depression, diabetes, and schizophrenia. Early this year the firm received a one-year, $300,000 grant from the Michael J. Fox Foundation to support the further preclinical development of metabotrophic glutamate receptor 3 positive allosteric modulators against Parkinson’s disease. 

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