Crowdsourced identification of multi-target kinase inhibitors for RET- and TAU- based disease: The Multi-Targeting Drug DREAM Challenge

Zhaoping Xiong, Minji Jeon, Robert J. Allaway, Jaewoo Kang, Donghyeon Park, Jinhyuk Lee, Hwisang Jeon, Miyoung Ko, Hualiang Jiang, Mingyue Zheng, Aik Choon Tan, Xindi Guo, Multi-Targeting Drug DREAM Challenge Community, Kristen K. Dang, Alex Tropsha, Chana Hecht, Tirtha K. Das, Heather A. Carlson, Ruben Abagyan, Justin Guinney et al. (2 additional authors not shown)

Abstract: Author summary Many modern drugs are developed with the goal of modulating a single cellular pathway or target. However, many drugs are, in fact, ‘dirty;’ they target multiple cellular pathways or targets. This phenomenon is known as multi-targeting or polypharmacology. While some strive to develop ‘cleaner’ therapeutics that eliminate secondary targets, recent work has shown that multi-targeting therapeutics have key advantages for a variety of diseases. However, while multi-targeting drugs that affect a precisely-defined profile of targets may be more effective, it is difficult to computationally predict which molecules have desirable target profiles. Here, we report the results of a competitive crowdsourcing project (the Multi-Targeting Drug DREAM Challenge), where we challenged participants to predict chemicals that have desired target profiles for cancer and neurodegenerative disease.