Combatting cancer is one of the biggest challenges for improving good health and well-being. Novel anticancer drug candidates have been approved over the last few years, yet many cancers remain as unmet medical needs. Achieving a superior understanding of the molecular mechanism of anticancer drugs is key for designing and developing better compounds in terms of potency and safety profiles. Structural biology and computational studies can help remarkably to investigate the mechanism of action of anticancer drugs. Here, we combine X-ray crystallography with molecular dynamics to investigate structural and energetic properties of drug candidates binding to tubulin, a validated target for the discovery of anticancer medicines. In particular, we study plinabulin, colchicine, and combretastatin-A4, analyzing their mechanism of binding to tubulin, which potentially explains their different functional and safety profiles. We further provide a protocol to study novel tubulin-targeted drugs.
Structure, Thermodynamics, and Kinetics of Plinabulin Binding to Two Tubulin Isotypes / La Sala G.; Olieric N.; Sharma A.; Viti F.; de Asis Balaguer Perez F.; Huang L.; Tonra J.R.; Lloyd G.K.; Decherchi S.; Diaz J.F.; Steinmetz M.O.; Cavalli A.. - In: CHEM. - ISSN 2451-9308. - STAMPA. - 5:11(2019), pp. 2969-2986. [10.1016/j.chempr.2019.08.022]
Structure, Thermodynamics, and Kinetics of Plinabulin Binding to Two Tubulin Isotypes
La Sala G.;Sharma A.;Viti F.;Huang L.;Cavalli A.
2019
Abstract
Combatting cancer is one of the biggest challenges for improving good health and well-being. Novel anticancer drug candidates have been approved over the last few years, yet many cancers remain as unmet medical needs. Achieving a superior understanding of the molecular mechanism of anticancer drugs is key for designing and developing better compounds in terms of potency and safety profiles. Structural biology and computational studies can help remarkably to investigate the mechanism of action of anticancer drugs. Here, we combine X-ray crystallography with molecular dynamics to investigate structural and energetic properties of drug candidates binding to tubulin, a validated target for the discovery of anticancer medicines. In particular, we study plinabulin, colchicine, and combretastatin-A4, analyzing their mechanism of binding to tubulin, which potentially explains their different functional and safety profiles. We further provide a protocol to study novel tubulin-targeted drugs.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
