TP0591108

TP0591108 is a novel, orally active dual antagonist of lysophosphatidic acid receptors 1 (LPA1) and 3 (LPA3) being developed by Taisho Pharmaceutical. It is designed to treat systemic sclerosis by addressing both tissue fibrosis and skin inflammation. While LPA1 is primarily expressed in fibroblasts and involved in fibrotic pathways, LPA3 is highly expressed in keratinocytes and contributes to skin homeostasis and inflammation. By antagonizing both receptors, TP0591108 aims to provide superior therapeutic efficacy compared to selective LPA1 antagonists. Preclinical studies in bleomycin-treated and tight-skin (TSK-1) mouse models have demonstrated that TP0591108 significantly reduces skin collagen overproduction and suppresses inflammatory/fibrosis-related gene expression more effectively than selective LPA1 inhibitors.