Drug Discovery

Discovery of Pre-Clinical Candidate Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist HTL0022562

By John Christopher | Sep 13, 2019


20th SCI / RSC Medicinal Chemistry Symposium

8 – 11 September 2019

Cambridge, UK

SCI, Royal Society of Chemistry

Presentation Summary

Blockade of the Calcitonin Gene-Related Peptide Receptor (CGRP) is a clinically validated mechanism for the treatment of migraine. Whilst the first mAbs have been recently approved the identification of small molecule CGRP antagonists remains an active and highly competitive area with several agents in clinical trials.

The presentation includes a first disclosure of the Sosei Heptares preclinical candidate HTL0022562, showcasing the use of X-ray crystallography for GPCR drug discovery and describes the use of Structure Based Drug Design (SBDD) to identify a structurally innovative class of ligands. HTL0022562 is a highly differentiated CGRP antagonist preclinical candidate identified using SBBD and biophysical methods. Data supporting slow off-rate kinetics, extremely high free drug potency and a very low dose human PK prediction with the potential for relevant CNS penetration are outlined.

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