Microtubulin binding sites as target for developing anticancer agents.
Article Details
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Islam MN, Iskander MN
Microtubulin binding sites as target for developing anticancer agents.
Mini Rev Med Chem. 2004 Dec;4(10):1077-104.
- PubMed ID
- 15579115 [ View in PubMed]
- Abstract
Microtubules (MTs) play important and diverse roles in eukaryotic cells. Their function and biophysical properties have made alpha-and beta-tubulin, the main components of MTs, the subject of intense study. Interfering with normal MT dynamics, for example, by the addition of tubulin ligands, can cause the cell great distress and affect MT stability and functions, including mitosis, cell motion and intracellular organelle transport. It has been shown in the literature that tubulin is an important target molecule for developing anticancer drugs. Tubulin binding molecules have generated considerable interest after the successful introduction of the taxanes into clinical oncology and the widespread use of the vinca alkaloids vincristine and vinblastine. These compounds inhibit cell mitosis by binding to the protein tubulin in the mitotic spindle and preventing polymerization into the MTs. This mode of action is also shared with other natural agents eg colchicine and podophyllotoxin. However various tubulin isotypes have shown resistance to taxanes and other MT agents. Therefore, there is a strong need to design and develop new natural analogs as antimitotic agents to interact with tubulin at sites different from those of vinca alkaloids and taxanes. This minireview provides SAR on several classes of antimitotic agents reported in the literature. The structures and data given are essential to the scientists who are involved in drug design and development in the field of anticancer drugs.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Vinblastine Tubulin alpha-1A chain Protein Humans YesBinderDetails Vinblastine Tubulin beta chain Protein Humans YesBinderDetails Vinblastine Tubulin delta chain Protein Humans YesBinderDetails Vinblastine Tubulin epsilon chain Protein Humans YesBinderDetails Vinblastine Tubulin gamma-1 chain Protein Humans YesBinderDetails