Press release
May 31, 2017

Sosei Subsidiary Heptares Solves First Full-length Structure of GLP-1 Receptor Bound to Peptide Agonist

New findings highlight complexity of receptor interactions and provide crucial insights for development of peptide and small molecule therapeutics – research published in Nature

Tokyo, Japan –31 May 2017: Sosei Group Corporation (“Sosei”; TSE Mothers Index: 4565) today reports that Heptares Therapeutics (“Heptares”), its wholly-owned subsidiary, has published the first high-resolution X-ray crystal structure of the full-length glucagon-like peptide-1 (GLP-1) receptor bound to a peptide agonist.

The findings, published in Nature, provide insight to the molecular mechanism of action of GLP-1 peptides and their interactions with the receptor. Importantly, this pioneering research further validates and enables the application of structure-based methods to the design of optimised peptide therapeutics and small molecules targeting the GLP-1 receptor, and related G protein-coupled receptors (GPCRs), for treating a range of diseases. The research was published online in Nature today and can be accessed at

GLP-1 is an important peptide hormone that regulates glucose homeostasis through control of insulin release from the pancreas. Activating the GLP-1 receptor is one of the most important and highly validated mechanisms for treating Type 2 diabetes, and awareness is increasing about the potential of this target in treating other metabolic diseases, as well as cardiovascular and neurological diseases. A number of GLP-1 peptide agonists, with improved stability and duration of action compared to native GLP-1, are already approved for treating Type 2 diabetes, including exenatide (Byetta®/Bydureon®), liraglutide (Victoza®, Saxenda®), lixisenatide (Lyxumia®), albiglutide (Tanzeum®) and dulaglutide (Trulicity®).

Fiona Marshall, Chief Scientific Officer of Heptares and Sosei, said: “The findings from this research at Heptares are ground-breaking and very exciting: they unveil a remarkably complex network of interactions between GLP-1 peptide ligands and the receptor that explains why it has been so difficult to mimic this effect with a small molecule. Understanding these interactions at a molecular level may be the breakthrough that enables the design of small molecule drugs, as well as optimised therapeutic peptides, targeting not only the GLP1 receptor but also other closely related GPCR targets implicated in many diseases.”

The GLP-1 receptor is a member of the Class B secretin group of GPCRs, a family of structurally similar receptors for peptide hormones such as GLP-1, glucagon, corticotropinreleasing factor (CRF), calcitonin and parathyroid peptide hormone. Class B GPCRs include many therapeutic targets for cardiovascular diseases, metabolic diseases, bone diseases and migraine, but despite strong clinical validation, structural information is limited.

Reference Jazayeri, A et al. Crystal structure of the GLP-1 receptor bound to a peptide agonist (2017) Nature