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Selective, covalent modification of β-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors
Open accessAbstract
Microtubules are linear polymers of α- and β-tubulin heterodimers and are the major constituents of mitotic spindles, which are essential for the separation of chromosomes during mitosis. Here we describe a synthetic compound, 2-fluoro-1-methoxy-4-pentafluorophenylsulfonamidobenzene (T138067), which covalently and selectively modifies the β 1 , β 2 , and β 4 isotypes of β-tubulin at a conserved cysteine residue, thereby disrupting microtubule polymerization. Cells exposed to T138067 become altered in shape, indicating a collapse of the cytoskeleton, and show an increase in chromosomal ploidy. Subsequently, these cells undergo apoptosis. Furthermore, T138067 exhibits cytotoxicity against tumor cell lines that exhibit substantial resistance to vinblastine, paclitaxel, doxorubicin, and actinomycin D. T138067 is also equally efficacious in inhibiting the growth of sensitive and multidrug-resistant human tumor xenografts in athymic nude mice. These observations suggest that T138067 may be clinically useful for the treatment of multidrug-resistant tumors.
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Citations
Cited by
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Metadata
- Authors
- Shan, B., Medina, J. C., Santha, E., Frankmoelle, W. P., Chou, T.-C., Learned, R. M., Narbut, M. R., Stott, D., Wu, P., Jaen, J. C., Rosen, T., Timmermans, P. B. M. W. M., & Beckmann, H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-05-11
- Volume
- 96
- Issue
- 10
- Pages
- 5686-5691
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2101600612
- Cited by
- 164
- References
- 0
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Selective, covalent modification of β-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors. https://app.cochat.ai/papers/10.1073/pnas.96.10.5686
- The paper
- Shan, B., Medina, J. C., Santha, E., Frankmoelle, W. P., Chou, T.-C., Learned, R. M., Narbut, M. R., Stott, D., Wu, P., Jaen, J. C., Rosen, T., Timmermans, P. B. M. W. M., & Beckmann, H. (1999). Selective, covalent modification of β-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.10.5686
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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