Summary
The subunit protein of microtubules is tubulin, which has been the target for some of the most successful and widely used anti-tumor drugs. Most of the drugs that target tubulin bind to the β subunit. There are many isotypes of β-tubulin and their distributions differ among different tissues. The βIII isotype is over-expressed in many tumors, particularly those that are aggressive, metastatic, and drug resistant. We have previously reported the design and synthesis of a series of compounds to fit the colchicine site on βIII but not on the other isotypes. In the current study, we tested the toxicity and the anti-tumor activity of one of these compounds, CH-35, on the human breast tumor MDA-MB-231 over-expressing βIII in a xenogeneic mouse model. We found that CH-35 was as toxic as Taxol® in vivo. Although the βIII-over-expressing cells developed into very fast-growing tumors, CH-35 was more effective against this tumor than was Taxol. Our results suggest that CH-35 is a promising candidate for future drug development.
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We acknowledge the support by US Army Medical Research grants W81XWH-10-1-0904 (BC097712 and BC097712P1) to RFL and JCL, respectively.
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Yeh, LC.C., Banerjee, A., Prasad, V. et al. Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the βIII isotype of tubulin. Invest New Drugs 34, 129–137 (2016). https://doi.org/10.1007/s10637-015-0315-6
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DOI: https://doi.org/10.1007/s10637-015-0315-6