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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References |
1. Kuo TC, Li LW, Pan SH, Fang JM, Liu JH, Cheng TJ, Wang CJ, Hung PF, Chen HY, Hong TM et al.. (2016)
Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin. J Med Chem, 59 (18): 8521-34. [PMID:27536893] |