2. Academic Validation
  3. Recent Progress on Tubulin Inhibitors with Dual Targeting Capabilities for Cancer Therapy

Recent Progress on Tubulin Inhibitors with Dual Targeting Capabilities for Cancer Therapy

  • J Med Chem. 2021 Jun 24;64(12):7963-7990. doi: 10.1021/acs.jmedchem.1c00100.
Wen Shuai 1,  Guan Wang 1,  Yiwen Zhang 1,  Faqian Bu 1,  Sicheng Zhang 2,  Duane D Miller 2,  Wei Li 2,  Liang Ouyang 1,  Yuxi Wang 1 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, Innovation Center of Nursing Research, National Clinical Research Center for Geriatrics, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, China.
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.
  • 3 Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
  • 4 Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
PMID: 34101463 DOI: 10.1021/acs.jmedchem.1c00100
Abstract

Microtubules play a crucial role in multiple cellular functions including mitosis, cell signaling, and organelle trafficking, which makes the microtubule an important target for Cancer therapy. Despite the great successes of microtubule-targeting agents in the clinic, the development of drug resistance and dose-limiting toxicity restrict their clinical efficacy. In recent years, multitarget therapy has been considered an effective strategy to achieve higher therapeutic efficacy, in particular dual-target drugs. In terms of the synergetic effect of tubulin and Other antitumor agents such as Receptor Tyrosine Kinases inhibitors, histone deacetylases inhibitors, DNA-damaging agents, and Topoisomerase inhibitors in combination therapy, designing dual-target tubulin inhibitors is regarded as a promising approach to overcome these limitations and improve therapeutic efficacy. In this Perspective, we discussed rational target combinations, design strategies, structure-activity relationships, and future directions of dual-target tubulin inhibitors.

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