Polyphenol MHQP as an allosteric inhibitor of Kinesin-5: Cease the molecular catwalk of “Drunken Sailor”

Human Kinesin-5 (KIF-11/Eg5), a major anticancer drug target, is plus end-directed motor protein that involved in spindle dynamics and principally mitosis. In the present study, computer-aided rational discovery approach has been applied to search for potential allosteric inhibitors against Eg5. Accordingly, virtual screening of naturally occurring secondary metabolites their commercially available synthetic derivatives indicates 2-(9b- methyl-2,3,3a,4,5,9b-hexahydrofuro [3,2 c] quinolin-4-yl) phenol (MHQP), hexahydrofuro [3,2-c] quinolone derivative as therapeutic lead molecule The study provides structural glimpse MHQP binding at monastrol site Eg5 with vivid description its plausible mode inhibition. Moreover, silico data also supports superiority over well-characterized inhibitor Arry-520 terms augmented affinity well cope resistant mutants Structure-guided mechanistic details MHQP-induced inhibition predicted pharmacodynamics properties have presented herein.