It is well documented in literature that activation of RXFP1 by relaxin induces: 1) up-regulation of the endothelin system which leads to vasodilation; 2) extracellular matrix remodeling through regulation of collagen deposition, cell invasiveness, proliferation, and overall tissue homeostasis; 3) a moderation of inflammation by reducing levels of inflammatory cytokines, such as TNF-a and TGF-b; and 4) angiogenesis by activating transcription of VEGF.

The present invention is directed to novel relaxin receptor (RFXP1 receptor) small molecule agonists useful for treating relaxin-related disorders including fibrosis, certain cancers, vascular calcifications, including atherosclerosis, and heart failure. The RFXP1 agonists of this disclosure possess a number of advantages not found in earlier RFXP1 agonists. These properties include, for example, improved bioavailability, low toxicity, and better activity in RXFP1-dependent biological functional assays.

NCATS in collaboration with Florida International University (FIU) and University of South Florida (USF) has identified low molecular weight, highly potent, and efficient full RXFP1 agonists with low cytotoxicity. The identification and characterization of these compounds may lead to the development of a new class of cost-effective drugs for the treatment of numerous cancers, fibrotic, and vascular disorders.

NCATS is actively seeking licensing to develop therapeutic interventions for cancers, fibrotic and vascular disease including but not limited to breast cancer, solid tumors, atherosclerosis, and liver fibrosis.