Summary Receptor tyrosine kinases (RTKs) modulate a
variety of cellular events, including cell proliferation, differ-
entiation, mobility and apoptosis. In addition, RTKs have
been validated as targets for cancer therapies. Microtubules
are another class of proven targets for many clinical anticancer
drugs. Here, we report that 1-(4-chloro-3-(trifluoromethyl)
phenyl)-3-(2-cyano-4-hydroxyphenyl)urea (D181) functions
as both a receptor tyrosine kinase inhibitor and a tubulin
polymerization enhancer. D181 displayed potent inhibitory
activities against a panel of RTKs, including Flt3, VEGFR,
cKit, FGFR1 and PDGFRβ. D181 also enhanced tubulin
polymerization and modified the secondary structure of
tubulin proteins to disrupt their dynamic instability. Because
of synergistic cooperation, D181 strongly inhibited the
proliferation of various cancer cell lines, induced LoVo cell
cycle arrest in the G1 and M phases and suppressed tumor
growth in nude mice bearing human LoVo and HT29
xenografts. Our studies have provided a new, promising lead
compound and novel clues for multi-target anticancer drug
design and development.