Compound class:
Synthetic organic
Comment: Compound 5a causes microtubule fragmentation via modulation of the hydrolase activity of katanin [1]. The precise binding site has not been determined, but could reside within catalytic site of KATNA1 (p60 subunit) due to the purine scaffold of 5a. A docking model suggests that 5a may bind in a position which stabilizes the p60 structure and enhances the microtubule severing activity of katanin.
Katanin-modulating compounds could provide an alternative to vinca alkaloid and taxane microtubule targeting agents (MTAs), which suffer from issues of drug-induced resistance developing in clinical use. |
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Bioactivity Comments |
Compound 5a-induced microtubule fragmentation leads to G2/M cell cycle arrest and intrinsic apoptosis in lung cancer cells with growth-inhibitory IC50s for several cell lines between 230-330nM [1]. |