title: Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials.
abstract: A number of chemically diverse substances bind to the tubulin and inhibit cell proliferation by disrupting microtubule dynamics. There are four binding sites for the ligands binding to the tubulin; taxane/epothilone and laulimalide/peloruside binding ligands stabilize microtubule while vinca and colchicine binding site agents promote microtubule depolymerization. Most of the tubulin binding ligands disturb the tubulin-microtubule dynamic equilibrium but these may exhibit anticancer activities through different mechanisms. Taxanes and epothilones are widely used cytotoxic agents and are found effective against different types of human malignancies. However, taxanes are susceptible to pgp mediated multi-drug resistance, dose limiting hematopoietic toxicity and cumulative neurotoxicity. Vinca alkaloids are already in clinical practice, but ligands binding to the colchicine site are still in the different stages of clinical trials.
  
  
  
  In the current review article, plausible mechanistic details about the interactions of ligands at the binding pocket and subsequent changes in the tubulin structure are described. The review article also illustrated different formulations of the tubulin binding agents in combination with other chemotherapeutic agents and their therapeutic potential against various human malignancies.
  
  
  
  Tubulin targeting agents emerged as one of the most successful anticancer drugs and a number of structurally different chemical compounds are in advance stages of clinical development.
authors.affiliation: Laboratory of Organic and Medicinal Chemistry, Centre for Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Kumar
authors.affiliation: Laboratory of Organic Chemistry, Centre for Chemical Sciences, Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Laboratory for Experimental and Translational Research on Radiation Oncology (EXTRO-Lab), Department of Therapeutic Radiology and Oncology, Innsbruck Medical University, Anichstr. 35, A-6020 Innsbruck. Austria.
authors.forename: Ira
authors.initials: I
authors.lastname: Skvortsova
authors.affiliation: Laboratory of Organic and Medicinal Chemistry, Centre for Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
mesh_terms: D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008870:Microtubules / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058105:Polymerization; D014404:Tubulin / Q000378:metabolism*
chemical_list: D008024:Ligands; D014404:Tubulin
keywords: Tubulin inhibitor; anticancer; combination
  therapy; microtubule stabilizing agents; tubulin binding ligands; tubulin polymerization/depolymerization