Targeting the relaxin/insulin-like family peptide receptor 1 and 2 with small molecule compounds. (1st May 2019)

• Record Type: Journal Article
• Authors: Ng, Hooi Hooi; Esteban-Lopez, Maria; Agoulnik, Alexander I.
• Is Part Of: Molecular and cellular endocrinology. Volume 487(2019)
• Page Start: 40
• Page End: 44
• Publication Date: 2019-05-01
• Subjects: RXFP1 -- RXFP2 -- G protein-coupled receptor -- ML290 -- Relaxin -- Small molecule agonist; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.12.013
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The peptide hormone relaxin has beneficial roles in several organs through its action on its cognate G protein-coupled receptor, RXFP1. Relaxin administration is limited to intravenous, subcutaneous, intramuscular, or spinal injection. Another drawback of peptide-based therapy is the short half-life, which requires continuous delivery of the drug to achieve efficient concentration in target organs. The discovery of a non-peptide small molecule agonist of RXFP1, ML290, provides an alternative to the natural ligand. This review summarizes the development of ML290 and its potential future therapeutic applications in various diseases, including liver fibrosis and cardiovascular diseases. We also discuss the development of small molecule agonists targeting the insulin-like 3 receptor, RXFP2, and propose the potential use of these small molecules in the context of bone and muscle remodeling. Highlights: Availability of a unique human RXFP1 mouse strain for preclinical studies. Distinct cellular signaling pathways mediated by a biased allosteric agonist of RXFP1, ML290. Screening efforts for small molecule compounds targeting RXFP2.