Endocrine Abstracts

The beneficial effects of relaxin peptide treatment have been demonstrated in animal models of liver fibrosis. However, the low stability of peptide in vivo prevents using it in chronic treatments. We have identified a series of small molecule allosteric agonists of the human relaxin receptor, RXFP1. The therapeutic effects of lead compound ML290 was tested in various models of liver fibrosis. To analyze the anti-fibrotic effects of ML290 on gene expression, we used p...

Androgen receptor (AR) signaling is the main driver for prostate cancer progression and androgen ablation is the treatment of choice for tumors that spread beyond the prostate. Efficient at first, androgen ablation fails due in part to altered cell signaling and expression of AR spice variants. Cell signaling in prostate cancer is regulated by dual specificity phosphatases and tumor suppressors INPP4B and PTEN that are lost with prostate cancer progression. Loss of PTEN destab...

The anti-fibrotic, vasodilatory, and angiogenic therapeutic properties of relaxin peptide have been shown in several animal models of human diseases and in clinical trials. Using high-throughput screening of small molecule library, structure-activity relationship (SAR) studies, ligand-receptor interaction modeling, site-specific mutagenesis, and transgenic animal studies we discovered the first series of small molecule agonists of relaxin GPCR, RXFP1. The lead compound ML290 i...