Kinase inhibitors: not just for kinases anymore.

Article Details


McGovern SL, Shoichet BK

Kinase inhibitors: not just for kinases anymore.

J Med Chem. 2003 Apr 10;46(8):1478-83.

PubMed ID
12672248 [ View in PubMed

Kinase inhibitors are widely employed as biological reagents and as leads for drug design. Their use is often complicated by their lack of specificity. Although binding conserved ATP sites accounts for some of their nonspecificity, some compounds inhibit proteins not known to bind ATP. It has been found that promiscuous hits from high-throughput screening may act as aggregates. To explore whether this mechanism might explain the action of widely used nonspecific kinase inhibitors, 15 such compounds were studied. Eight of these, rottlerin, quercetin, K-252c, bisindolylmaleimide I, bisindolylmaleimide IX, U0126, indirubin, and indigo, inhibited three diverse non-kinase enzymes. Inhibition was time-dependent and sensitive to enzyme concentration; by light scattering, the compounds formed particles of 100-1000 nm diameter. These observations suggest that these eight kinase inhibitors, at least at micromolar concentrations, are promiscuous and act as aggregates. Results obtained from the use of these compounds at micromolar or higher concentrations against individual enzymes should be interpreted cautiously.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
FasudilRho-associated protein kinase 2IC 50 (nM)1900N/AN/ADetails
Y-27632Rho-associated protein kinase 2IC 50 (nM)700N/AN/ADetails