CHISHIKI

Development

Identification and characterisation of a novel GLP-1 receptor antagonist peptide HTL0033097

By Alastair Brown | Mar 29, 2022

Alastair Brown, VP Translational Sciences at Sosei Heptares presented a poster at the American Chemical Society (ACS) Spring 2022 meeting, describing the design strategy and pharmacodynamic evaluation of HTL0033097, a novel selective GLP-1 antagonist.

 

Abstract

  • Hypoglycaemia as a result of excessive insulin secretion from the pancreatic b-cell is a rare but serious condition that if left untreated can result in cognitive impairment, loss of consciousness, seizures and in infants the risk of permanent brain damage.  Hyperinsulinemic hypoglycaemia (HI) is the hallmark of a number of rare disorders including congenital hyperinsulinism (CHI) and post-bariatric hypoglycaemia (PBSH). Blocking the GLP-1 system will have direct effects on insulin secretion and result in normalisation of conditions associated with HI. 
  • This work outlines the application of a robust structural understanding of the GLP-1 peptide binding pocket to design a highly selective GLP-1 antagonist peptide (HTL0033097), which demonstrated significant improved pharmacokinetic and pharmacodynamic properties compared to Ex9-39.

 

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