Poster Presentation 7th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2019

Development of novel G-protein coupled receptor, RXFP1, antagonists to treat cancer   (#126)

Praveen Praveen 1 , Ross Bathgate 1 , M. Akhter Hossain 1
  1. Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia

Relaxin is a pleiotropic hormone which exerts its biological functions through its G-protein coupled receptor, RXFP1. While relaxin is well known for its reproductive and antifibrotic roles, recent studies suggest that it is produced by cancer cells and acts on RXFP1 to induce growth and metastasis. Recently, a relaxin analog (B-R13/17K H2) was developed that was shown to reduce the growth of prostate xenograft tumors. However, this analog has two-chain and three disulfides bonded structure which is low yielding and expensive to manufacture. We carried out extensive structure-function studies to determine the residues involved in agonism and antagonism functions.  We report here the development of high yielding relaxin analogs that act as antagonists. These analogs can now be used as tools to further understand RXFP1 function, and serve as templates for drug design for a therapeutic to treat prostate and other cancers.