title: The hunt for antimitotic agents: an overview of structure-based design strategies.
abstract: BACKGROUND
  Structure-based drug discovery offers a rational approach for the design and development of novel anti-mitotic agents which target specific proteins involved in mitosis. This strategy has paved the way for development of a new generation of chemotypes which selectively interfere with the target proteins. The interference of these anti-mitotic targets implicated in diverse stages of mitotic cell cycle progression culminates in cancer cell apoptosis.
  
  
  METHODS
  This review covers the various mitotic inhibitors developed against validated mitotic checkpoint protein targets using structure-based design and optimization strategies. The protein-ligand interactions and the insights gained from these studies, culminating in the development of more potent and selective inhibitors, have been presented.
  
  
  CONCLUSIONS
  The advent of structure-based drug design coupled with advances in X-ray crystallography has revolutionized the discovery of candidate lead molecules. The structural insights gleaned from the co-complex protein-drug interactions have provided a new dimension in the design of anti-mitotic molecules to develop drugs with a higher selectivity and specificity profile. Targeting non-catalytic domains has provided an alternate approach to address cross-reactivity and broad selectivity among kinase inhibitors. The elucidation of structures of emerging mitotic drug targets has opened avenues for the design of inhibitors that target cancer.
authors.affiliation: a Department of Biophysics , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: D
authors.initials: D
authors.lastname: Dube
authors.affiliation: a Department of Biophysics , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: P
authors.initials: P
authors.lastname: Tiwari
authors.affiliation: a Department of Biophysics , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: P
authors.initials: P
authors.lastname: Kaur
mesh_terms: D050256:Antimitotic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D050256:Antimitotic Agents
keywords: Antimitotic; cancer therapy; kinase inhibitor; mitotic checkpoints; structure-based drug design