The high?resolution X?ray structure of vinca?domain inhibitors of microtubules provides a rational approach for drug design

Tubulin vinca-domain ligands can inhibit microtubule polymerization, causing cell death in mitosis, and their potential against multiple cancer types has been demonstrated. However, due to drug resistance toxicities, development of novel is still needed. In this study, we determined the high-resolution crystal structures vinorelbine, YXD, Phomopsin A complex with tubulin at 2.5 Å. Additionally, recapitulated all previously published vinca binding site reveal critical residues molecular mechanism interacting tubulin. Furthermore, designed putatively triazolopyrimidine derivatives by introducing secondary amine groups establish salt-bridge H-bond interactions Asp179?1 Asn329?2. Our studies provided structural basis for designing ligands.