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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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General Review Article

Tubulin Maytansine Site Binding Ligands and their Applications as MTAs and ADCs for Cancer Therapy

Author(s): Shuo Cao, Yue-Hui Dong, De-Feng Wang and Zhao-Peng Liu*

Volume 27, Issue 27, 2020

Page: [4567 - 4576] Pages: 10

DOI: 10.2174/0929867327666200316144610

Price: $65

Abstract

Background: Microtubule Targeting Agents (MTAs) represent the most successful anticancer drugs for cancer chemotherapy. Through interfering with the tubulin polymerization and depolymerization dynamics, MTAs influence intracellular transport and cell signal pathways, inhibit cell mitosis and cell proliferation, and induce cell apoptosis and death. The tubulin maytansine site binding agents are natural or nature-derived products that represent one type of the MTAs that inhibit tubulin polymerization and exhibit potent antitumor activity both in vitro and in vivo. They are used as Antibody-Drug Conjugates (ADCs) in cancer chemotherapy.

Methods: Using SciFinder® as a tool, the publications about maytansine, its derivatives, maytansine binding site, maytansine site binding agents and their applications as MTAs for cancer therapy were surveyed with an exclusion on those published as patents. The latest progresses in clinical trials were obtained from the clinical trial web.

Results: This article presents an introduction about MTAs, maytansine, maytansine binding site and its ligands, the applications of these ligands as MTAs and ADCs in cancer therapy.

Conclusion: The maytansine site binding agents are powerful MTAs for cancer chemotherapy. The maytansine site ligands-based ADCs are used in clinic or under clinical trials as cancer targeted therapy to improve their selectivity and to reduce their side effects. Further improvements in the delivery efficiency of the ADCs will benefit the patients in cancer targeted therapy.

Keywords: Microtubule targeting agents, maytansine binding site, rhizoxin, plocabulin, antibody-drug conjugates, trastuzumab emtansine.

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