Identifying a novel anticancer agent with microtubule-stabilizing effects through computational cell-based bioactivity prediction models and bioassaysElectronic supplementary information (ESI) available: Comprehensive NCI-60 data set (ESI Table S1) and four independent external testing sets (ESI Table S4) and the 55 virtual hits (ESI Table S5) were purchased for experimental validation (XLSX). See DOI: 10.1039/c8ob02193g

• Main Authors: Luo, Yao, Zeng, Ranran, Guo, Qingqing, Xu, Jianrong, Sun, Xiaoou, Wang, Ling
• Format: Journal Article
• Published: 06.02.2019
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c8ob02193g

We report the identification of 14 novel anticancer agents through established computational anticancer cell-based models. Among these novel hits, the compound G03 exhibits stronger inhibitory effects on the proliferation of MCF-7, HepG2, MDA-MB-231, HCTT116, and HeLa as compared with the FDA-approved sorafenib, with IC 50 values of 4.61, 3.20, 2.82, 2.98, and 2.90 μM, respectively. The tubulin protein was validated to be a target of G03 using SPR, tubulin polymerization, immunofluorescence, and western blot assays. G03 is a novel structurally simple anticancer agent with unusual microtubule-stabilizing effects. Our study demonstrated the identification of bioactive small molecules by computational phenotypic modeling, which represents a feasible route toward innovative leads for chemical biology and medicinal chemistry. G03 is a novel anticancer agent with unusual microtubule-stabilizing effects.