Collaborative research from our laboratory, in 2010, produced a first-in-class inhibitor of BET bromodomain proteins (JQ1). As an effort to promote a more open-innovation model of drug discovery, we endeavored to provide JQ1 without restriction of cost or delay to the scientific community. Toward this objective, we have optimized and completed a facile scaling synthesis capable of producing 100 g quantities of the active (+)-JQ1 stereoisomer. In the past 30 months, JQ1 has been provided to over 350 laboratories in more than a dozen countries. Through this research, BET bromodomain proteins have emerged as pharmacologically validated targets in multiple model systems of cancer including squamous carcinoma of the lung, head and neck, acute myeloid leukemia, multiple myeloma, Burkitt lymphoma, B-cell acute lymphoblastic leukemia, neuroblastoma and non-small cell lung cancer. More than 800 cancer cell lines and 25 murine models of cancer have been systematically screened with JQ1 for sensitivity to bromodomain inhibition, identifying additional therapeutic opportunities. Open availability of JQ1 has also lead to unexpected innovation outside of cancer research through studies identifying opportunities for BET bromodomain inhibition in such diverse fields as male contraception and HIV therapeutics. Since publication of the chemical structure and synthetic route to JQ1, seven new BET bromodomain inhibitors have appeared in the literature each derivatized from and/or benchmarked to the JQ1 molecule. Importantly, BET bromodomain inhibition has already accomplished clinical translation. To more objectively assess the consequence of open-innovation as a model of drug discovery, we have systematically analyzed metadata collected from published research and our ongoing efforts in compound distribution. Here, we present an interim analysis which relates the effect of open-innovation in drug discovery to the scope, productivity, reproducibility and importantly the pace of scientific research in epigenetic reader proteins. These results identify open-innovation in drug discovery as a catalyst for scientific discovery, bridging a gap between fields of research and the basic and clinical sciences.

Citation Format: Daniel L. Shaw, Charles Y. Lin, Richard P. Oakley, Nicholas P. Semenkovich, Jun Qi, James E. Bradner. Open innovation drug discovery: A study in JQ1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-2. doi:10.1158/1538-7445.AM2013-LB-2