Recent advances in heterocyclic Tubulin inhibitors targeting the colchicine binding site

Xiaoxin Wu, Qinghui Wang, Wei Li

Research output: Contribution to journalReview article

27 Citations (Scopus)

Abstract

Microtubules are involved in many critical cellular processes including cell division, cell shape maintenance, vesicle transportation and motility regulation. Disruption of tubulin dynamics is a well-validated cancer drug target with several FDA approved, highly efficacious tubulin inhibitors targeting the taxane or the vinca binding sites. Despite the tremendous successes for these clinical tubulin inhibitors, their limitations are also apparent, particularly in the development of transporter mediated drug resistance. While currently there are no FDA approved inhibitors targeting the colchicine binding site in tubulin, extensive preclinical studies have suggested that colchicine binding site inhibitors (CBSIs) have significantly less susceptibility to transporter medicated drug resistance. The presence of one or more heterocyclic moieties is often critical for the antiproliferative activities for most of these CBSIs. This article aims to review the structures and antiproliferative activities of most recently developed heterocyclic CBSIs from 2013 to present. We focus this review on compounds that are designed based on the CA-4, chalcone and PTOX scaffolds which are well established to interact with the colchicine binding site in tubulin.

Original languageEnglish (US)
Pages (from-to)1325-1338
Number of pages14
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

Tubulin Modulators
Colchicine
Binding Sites
Tubulin
Drug Resistance
Vinca
Chalcone
Cell Shape
Microtubules
Cell Division
Maintenance
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology
  • Cancer Research

Cite this

Recent advances in heterocyclic Tubulin inhibitors targeting the colchicine binding site. / Wu, Xiaoxin; Wang, Qinghui; Li, Wei.

In: Anti-Cancer Agents in Medicinal Chemistry, Vol. 16, No. 10, 01.10.2016, p. 1325-1338.

Research output: Contribution to journalReview article

@article{234d8f5267cb4f4c91e9bf04fbb9b167,
title = "Recent advances in heterocyclic Tubulin inhibitors targeting the colchicine binding site",
abstract = "Microtubules are involved in many critical cellular processes including cell division, cell shape maintenance, vesicle transportation and motility regulation. Disruption of tubulin dynamics is a well-validated cancer drug target with several FDA approved, highly efficacious tubulin inhibitors targeting the taxane or the vinca binding sites. Despite the tremendous successes for these clinical tubulin inhibitors, their limitations are also apparent, particularly in the development of transporter mediated drug resistance. While currently there are no FDA approved inhibitors targeting the colchicine binding site in tubulin, extensive preclinical studies have suggested that colchicine binding site inhibitors (CBSIs) have significantly less susceptibility to transporter medicated drug resistance. The presence of one or more heterocyclic moieties is often critical for the antiproliferative activities for most of these CBSIs. This article aims to review the structures and antiproliferative activities of most recently developed heterocyclic CBSIs from 2013 to present. We focus this review on compounds that are designed based on the CA-4, chalcone and PTOX scaffolds which are well established to interact with the colchicine binding site in tubulin.",
author = "Xiaoxin Wu and Qinghui Wang and Wei Li",
year = "2016",
month = "10",
day = "1",
doi = "10.2174/1871520616666160219161921",
language = "English (US)",
volume = "16",
pages = "1325--1338",
journal = "Anti-Cancer Agents in Medicinal Chemistry",
issn = "1871-5206",
publisher = "Bentham Science Publishers B.V.",
number = "10",

}

TY - JOUR

T1 - Recent advances in heterocyclic Tubulin inhibitors targeting the colchicine binding site

AU - Wu, Xiaoxin

AU - Wang, Qinghui

AU - Li, Wei

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Microtubules are involved in many critical cellular processes including cell division, cell shape maintenance, vesicle transportation and motility regulation. Disruption of tubulin dynamics is a well-validated cancer drug target with several FDA approved, highly efficacious tubulin inhibitors targeting the taxane or the vinca binding sites. Despite the tremendous successes for these clinical tubulin inhibitors, their limitations are also apparent, particularly in the development of transporter mediated drug resistance. While currently there are no FDA approved inhibitors targeting the colchicine binding site in tubulin, extensive preclinical studies have suggested that colchicine binding site inhibitors (CBSIs) have significantly less susceptibility to transporter medicated drug resistance. The presence of one or more heterocyclic moieties is often critical for the antiproliferative activities for most of these CBSIs. This article aims to review the structures and antiproliferative activities of most recently developed heterocyclic CBSIs from 2013 to present. We focus this review on compounds that are designed based on the CA-4, chalcone and PTOX scaffolds which are well established to interact with the colchicine binding site in tubulin.

AB - Microtubules are involved in many critical cellular processes including cell division, cell shape maintenance, vesicle transportation and motility regulation. Disruption of tubulin dynamics is a well-validated cancer drug target with several FDA approved, highly efficacious tubulin inhibitors targeting the taxane or the vinca binding sites. Despite the tremendous successes for these clinical tubulin inhibitors, their limitations are also apparent, particularly in the development of transporter mediated drug resistance. While currently there are no FDA approved inhibitors targeting the colchicine binding site in tubulin, extensive preclinical studies have suggested that colchicine binding site inhibitors (CBSIs) have significantly less susceptibility to transporter medicated drug resistance. The presence of one or more heterocyclic moieties is often critical for the antiproliferative activities for most of these CBSIs. This article aims to review the structures and antiproliferative activities of most recently developed heterocyclic CBSIs from 2013 to present. We focus this review on compounds that are designed based on the CA-4, chalcone and PTOX scaffolds which are well established to interact with the colchicine binding site in tubulin.

UR - http://www.scopus.com/inward/record.url?scp=84986921881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986921881&partnerID=8YFLogxK

U2 - 10.2174/1871520616666160219161921

DO - 10.2174/1871520616666160219161921

M3 - Review article

VL - 16

SP - 1325

EP - 1338

JO - Anti-Cancer Agents in Medicinal Chemistry

JF - Anti-Cancer Agents in Medicinal Chemistry

SN - 1871-5206

IS - 10

ER -