The discovery of new therapeutics to treat fibrosis disease is a rapidly evolving area of scientific interest due to new mechanistic insights, high unmet medical need and novel anti-fibrotic medicines successfully advancing in clinical trials and onto the market. Fibrosis disease can manifest itself in almost all parts of the body, with skin, lung, liver and kidney fibrosis being most prevalent, and is the result of a dysfunctional wound healing process. The etiology of fibrosis is often complex or unknown, exemplified by disease such as idiopathic pulmonary fibrosis (IPF). Not unlike cancer, fibrosis is a progressive disease where multiple biological processes are in play, and as in the case of IPF often responsible for a very high mortality rate.<br/><br/>A number of different approaches to identify anti-fibrotic agents are currently under investigation by pharmaceutical companies, from small molecules to antibodies, as single entities or combinations, but clearly spanning a wide range of targets, reflecting multiple avenues with which to potentially treat fibrosis.<br/><br/>The fibrosis box is a curated set of 200 small molecules capturing a wide mix of biological targets postulated to have involvement in fibrosis pathways and disease. The toolbox has been generated from commercially available literature compounds to further understanding of fibrosis disease at the mechanistic level. It is thought that the toolbox be used initially in an exploratory setting but could later be refined to specific targets of interest after an initial wave of screening in relevant biological systems. The toolbox molecules can be used for example to assist with assay validation, assessment of biological targets, understanding tissue selectivity, through to chemical hit identification and start points for drug discovery programmes. It may be the case that multiple mechanisms need to be engaged to successfully treat fibrosis and the toolbox is also perfectly placed for combinations of molecules to be tested. Ultimately, the toolbox could lead to raising interest in targets for fibrosis not currently being prosecuted in a drug discovery setting. Additional uses and collaborations are being explored and a review of the toolbox has been submitted to NRDD outlining clinical and exploratory molecules being progressed to treat fibrosis disease.

Fibrosis toolbox: Small molecules to investigate fibrosis pathways and mechanisms

249th National Meeting (2015)

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