+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Microtubule-stabilizing agents: New drug discovery and cancer therapy



Microtubule-stabilizing agents: New drug discovery and cancer therapy



Pharmacology and Therapeutics 162: 134-143



Microtubule-stabilizing agents (MSAs) have been highly successful in the treatment of cancer in the past 20years. To date, three classes of MSAs have entered the clinical trial stage or have been approved for clinical anticancer chemotherapy, and more than 10 classes of novel structural MSAs have been derived from natural resources. The microtubule typically contains two MSA-binding sites: the taxoid site and the laulimalide/peloruside site. All defined MSAs are known to bind at either of these sites, with subtle but significant differences. MSAs with different binding sites may produce a synergistic effect. Although having been extensively applied in the clinical setting, paclitaxel and other approved MSAs still pose many challenges such as multidrug resistance, low bioavailability, poor solubility, high toxicity, and low passage through the blood-brain barrier. A variety of studies focus on the structure-activity relationship in order to improve the pharmaceutical properties of these agents. Here, the mechanisms of action, advancements in pharmacological research, and clinical developments of defined MSAs during the past decade are discussed. The latest discovered MSAs are also briefly introduced in this review. The increasing number of natural MSAs indicates the potential discovery of more novel, natural MSAs with different structural bases, which will further promote the development of anticancer chemotherapy.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058315480

Download citation: RISBibTeXText

PMID: 26706241

DOI: 10.1016/j.pharmthera.2015.12.006


Related references

Discovery of new microtubule stabilizing agents from a marine sponge. Proceedings of the American Association for Cancer Research Annual Meeting 39: 166, 1998

Microtubule Targeting Agents as Cancer Chemotherapeutics: An Overview of Molecular Hybrids as Stabilizing and Destabilizing Agents. Current Topics in Medicinal Chemistry 17(22): 2523-2537, 2017

Microtubule stabilizing agents: their molecular signaling consequences and the potential for enhancement by drug combination. Cancer Treatment Reviews 32(3): 166-179, 2006

The synthesis, discovery, and development of a highly promising class of microtubule stabilizing agents: curative effects of desoxyepothilones B and F against human tumor xenografts in nude mice. Proceedings of the National Academy of Sciences of the United States of America 98(14): 13-18, 2001

Proteomics of cancer cell lines resistant to microtubule-stabilizing agents. Molecular Cancer Therapeutics 13(1): 260-269, 2014

Peloruside A synergizes with other microtubule stabilizing agents in cultured cancer cell lines. Molecular Pharmaceutics 4(2): 269-280, 2007

3-d QSAR studies of microtubule stabilizing antimitotic agents towards six cancer cell lines. QSAR and Combinatorial Science 25(10): 952-960, 2006

Cancer Drug Discovery and Development Series, 3; Antiangiogenic agents in cancer therapy. Teicher, B A Cancer Drug Discovery and Development Series, 3; Antiangiogenic agents in cancer therapy xiii+450p, 1999

Pharmacophore model generation for microtubule-stabilizing anti-mitotic agents (MSAAs) against ovarian cancer. Medicinal Chemistry Research 22(9): 4322-4330, 2013

Differential response to microtubule stabilizing agents of ovarian cancer cells harboring hot spot mutations of p53. Gynecologic Oncology 136(2): 401-402, 2015

Hallmarks of molecular action of microtubule stabilizing agents: effects of epothilone B, ixabepilone, peloruside A, and laulimalide on microtubule conformation. Journal of Biological Chemistry 286(13): 11765-11778, 2011

Miniaturization and validation of a sensitive multiparametric cell-based assay for the concomitant detection of microtubule-destabilizing and microtubule-stabilizing agents. Journal of Biomolecular Screening 11(4): 377-389, 2006

Modulation of lateral and longitudinal interdimeric interactions in microtubule models by Laulimalide and Peloruside A association: A molecular modeling approach on the mechanism of microtubule stabilizing agents. Chemical Biology and Drug Design 91(5): 1042-1055, 2018

Analysis of alpha- and beta-tubulin content by LC-MS and IEF in human cancer cell lines sensitive and resistant to microtubule-stabilizing agents. Proceedings of the American Association for Cancer Research Annual Meeting 43: 788, 2002

Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents. Breast Cancer Research 17: 59, 2016