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ECB-ART-42148
Bioorg Med Chem 2011 Sep 15;1918:5446-53. doi: 10.1016/j.bmc.2011.07.054.
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Synthesis and characterization of tritylthioethanamine derivatives with potent KSP inhibitory activity.

Rodriguez D , Ramesh C , Henson LH , Wilmeth L , Bryant BK , Kadavakollu S , Hirsch R , Montoya J , Howell PR , George JM , Alexander D , Johnson DL , Arterburn JB , Shuster CB .


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Assembly of a bipolar mitotic spindle requires the action of class 5 kinesins, and inhibition or depletion of this motor results in mitotic arrest and apoptosis. S-Trityl-l-cysteine is an allosteric inhibitor of vertebrate Kinesin Spindle Protein (KSP) that has generated considerable interest due to its anti-cancer properties, however, poor pharmacological properties have limited the use of this compound. We have modified the triphenylmethyl and cysteine groups, guided by biochemical and cell-based assays, to yield new cysteinol and cysteamine derivatives with increased inhibitory activity, greater efficacy in model systems, and significantly enhanced potency against the NCI60 tumor panel. These results reveal a promising new class of conformationally-flexible small molecules as allosteric KSP inhibitors for use as research tools, with activities that provide impetus for further development as anti-tumor agents.

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Genes referenced: LOC115919910

References [+] :
Al-Qawasmeh, Triaryl methane derivatives as antiproliferative agents. 2004, Pubmed