Expanding small-molecule target space to mRNA translation regulation.

Multiple layers of regulation are in place on mRNA translation to ensure that cells respond in a fast manner to environmental cues in a tissue-specific and mRNA-selective manner. Here, we discuss mRNA translation regulatory mechanisms and potential drug-intervention targets. Taking on a new scientific rational of translation regulation and consequently a new target space, we have developed a unique discovery platform that is able to identify selective small molecule drugs that affect translation of specific proteins. This approach has enabled targeting of proteins that have been considered undruggable. Our discovery platform was repeatedly utilized to identify compounds in multiple therapeutic programs, including fibrosis, oncology, anti-virals and Huntington's disease. In fibrosis, the lead compound ANI-21 has demonstrated a tissue-specific effect in lowering the translation of Collagen-I and superior efficacy over best standard of care, in both cell and animal models, mediated by a novel mechanism of action. This program is expected to enter clinical studies within 12-18 months.