Discovery of new core scaffold of Mer tyrosine kinase selective inhibitors by virtual screening / 国际药学研究杂志

Objective To discover the core structures for a series of new selective Mer tyrosine kinase inhibitors(TKI ) and design their compounds accordingly. Method The pharmacophore of the core domain was respectively generated by cocrystal of Mer tyrosine kinase (Mer TK) and bound inhibitors 1 (UNC569), 2 and 3 (PDB code: 3TCP, 4MHA and 4M3Q) and used to proceed virtual screening with online platform ZINCPharmer. Core structures were obtained after analyzing and classifying the virtual screening results and used for new inhibitors design. Results Totally 16 253 compounds were screened out, and classified to 12 core structures. Based on structure 12, 16a-16d were designed and docked with Mer TK. Among them, 16c exhibited the lowest binding energy, which could be used for future drug design. Concludsion A series of core structures keeping critical interaction with Mer TK are discovered and can be used for the new selective Mer TKI design and development. The procedure can also be applied to other targets drug discovery.

Discovery of new core scaffold of mer tyrosine kinase selective inhibitors by virtual screening / 国际药学研究杂志

Objective To discover the core structures for a series of new selective Mer tyrosine kinase inhibitor*(TKI) and design their compounds accordingly. Method The pharmacophore of the core domain was respectively generated by cocrystal of Mer tyrosine kinase (Mer TK) and bound inhibitors 1 (UNC569), 2 and 3 (PDB code: 3TCP, 4MHA and 4M3Q) and used to proceed virtual screening with online platform ZINCPharmer. Core structures were obtained after analyzing and classifying the virtual screening results and used for new inhibitors design. Results Totally 16 253 compounds were screened out, and classified to 12 core structures. Based on structure 12, 16a-16d were designed and docked with Mer TK. Among them, 16c exhibited the lowest binding energy, which could be used for future drug design. Concludsion A series of core structures keeping critical interaction with Mer TK are discovered and can be used for the new selective Mer TKI design and development. The procedure can also be applied to other targets drug discovery.