CHISHIKI

Drug Discovery

The Identification of GPR52 Agonist HTL0041178, a potential therapy for schizoaffective and related psychiatric disorders

By Steve Watson | Sep 22, 2021

About the Conference

21st RSC / SCI Medicinal Chemistry Symposium
13 -15 September 2021
Cambridge, UK

Conference Website

Summary

Steve Watson, Medicinal Chemistry Director at Sosei Heptares, recently attended the 21st RSC/SCI Medicinal Chemistry Symposium and presented “The Identification of GPR52 Agonist HTL0041178: A potential therapy for schizoaffective & related disorders” – the first public disclosure of HTL0041178.

Abstract

The G protein-coupled receptor (GPCR) superfamily encompasses a wealth of important drug targets and has historically yielded an extensive and diverse range of therapeutic agents. GPCRs are widely expressed in the central nervous system (CNS) and constitute the most common targets of neuropharmacological drugs, however there still remains considerable unrealised therapeutic potential for modulation of novel CNS GPCRs. Indeed, there are many orphan GPCRs expressed in the CNS for which disease association and therapeutic rationale is emerging, but which have yet to be drugged.

GPR52 is one such orphan GPCR. Based on expression, localisation, and in vivo studies with tool compounds a strong rationale for potentiation of the function of GPR52 as therapeutic intervention for schizoaffective and other neuropsychiatric disorders has emerged. Against this background the discovery of the GPR52 agonist candidate molecule HTL0041178 will be presented.

The presentation will describe the identification of novel lead start-points, a molecular property focussed strategy to optimise free receptor coverage, the establishment of PK/PD relationships, and the integration of human PK prediction into the molecule optimisation and selection strategy

Presentation Slides