Systemic sclerosis is a disease of uncertain cause characterized by collagen deposition and fibrosis in skin and internal organs including esophagus, lung, stomach, bowel, and joint. Systemic sclerosis is often progressive and accompanies fatal complications such as interstitial pneumonia and renal crisis.
Supportive treatment using steroid is the sole remedy at present; no drug to cure systemic sclerosis, unfortunately. Systemic sclerosis is classified as an incurable disease by Ministry of Health, Labor and Welfare, Japan.
Various important proteins have been identified to induce systemic sclerosis. However, realistic target for drug screening has not yet retrieved from many candidates. Thus, we carried out a phenotypic screening of inhibitors of transdifferentiation and fibrous focus formation and found a promising compoind HPH-15.
Abnormal deposition of collagen is the characteristic of systemic sclerosis. A cytokine TGF-β binds to the membrane receptor to induce Smad phosphorylation and collagen gene expression. Compound HPH-15 suppressed this and inhibited the collagen production.
Anticancer agent bleomycin (BLM) is known to have a diverse effect of fibrosis. Systemic sclerosisi model mouse is prepared by BLM injection to the back skin. Oral administration of HPH-15 ameliorated the skin thickness of this model mice. This is a joint research with Professor Hironobu Ihn, dermatology department of Kumamoto University, and Professor Minoru Haseawa, dermatology department of Fukui University.
HPH-15 is a promising compound as the first drug for systemic sclerosis.