Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge


Tubulin-Targeting Agents in Hybrid Drugs

Author(s): E. C. Breen and J. J. Walsh

Affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.

Keywords: Tubulin, microtubules, chemotherapy, combination therapy, resistance, hybrid, anti-cancer


The targeting of tubulin is an important mechanism for cancer chemotherapy. However, limitations such as resistance, toxicity and incomplete tumour elimination associated with individual anti-cancer drugs have led to a need for combination therapy in cancer. It is therefore relevant to ask whether two or more drugs might be combined in a single hybrid molecule to advantageous effect. This review provides an overview of the hybrid drugs thus far investigated, in which at least one component targets tubulin. The rationale behind this approach is that the hybrid drug may have activity enhanced above and beyond that of the equivalent drug combination, or have an otherwise improved clinical outcome. Particular emphasis is placed on the investigation of activity in multidrug-resistant cancer cell lines. Attention is drawn to the difficulties encountered when developing hybrid drugs, with respect to in vivo metabolism-tracking, increased molecular bulk, and optimisation of the drug dosage ratio. The actual and potential advantages and disadvantages of such hybrid drugs when compared to single drugs or drug combinations are discussed critically and promising directions for future research is highlighted.

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Article Details

Page: [609 - 639]
Pages: 31
DOI: 10.2174/092986710790416254