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A study is carried out on a synthetic analogue of the tripeptide hemiasterin (HTI-286) that depolymerizes microtubules is found to be poor substrate for P-glycoprotein and inhibits the growth of paclitaxel-resistant tumors in xenograft models. The results of the study suggest that hemiasterin is in close contact with alpha-tubulin and might span the interdiner interface.

Studies determine that HTI-286 is active against cell lines selected for paclitaxel or epothilone resistance and harboring point mutations in beta-tubulin at the taxane binding site. The difficulty in performing the selections, together with the occurrence of mutations only in regions of tubulin not associated with drug binding, as well as the absence of other resistance mechanisms, is viewed as favorable attributes for this class of drugs.