by Akao Y, Canan S, Cao Y, Condroski K, Engkvist O, Itono S, Kaki R, Kimura C, Kogej T, Nagaoka K, Naito A, Nakai H, Pairaudeau G, Radu C, Roberts I, Shimada M, Shum D, Watanabe N, Xie H, Yonezawa S, Yoshida O, Yoshida R, Mowbray C, Perry B. RSC Medicinal Chemistry 2021. doi: 10.1039/D0MD00353K
Summary: Since 2012, DNDi has tested over 2.2 million compounds in high throughput high content screening against kinetoplastid parasites in the search for novel small molecules as starting points for drug discovery campaigns. To improve the efficiency of triaging the results, the NTD drug discovery booster was created, a pre-competitive virtual screening model comprising key players from pharmaceutical R&D. In silico probing of five proprietary pharmaceutical company libraries enabled rapid expansion of an imidazo[1,2-a]pyridine screening hit for visceral leishmaniasis. Subsequent hit optimization informed by the structure–activity relationship enabled by this virtual screening allowed thorough investigation of the pharmacophore, opening avenues for further improvement and optimization of the chemical series.