Jm. Barret et al., INTEGRATED SYSTEM FOR THE SCREENING OF THE SPECIFICITY OF PROTEIN-KINASE INHIBITORS, Biochemical pharmacology, 46(3), 1993, pp. 439-448
Tyrosine protein kinases (TPKs) play a major role in the transformatio
n of cells. They are currently used as molecular targets for new gener
ations of anticancer compounds. Numerous TPKs have been described from
various tissues using either classical molecular biochemical techniqu
es or cloning strategies. As a natural extension of these discoveries,
a large number of ''specific'' inhibitors have been described in the
literature. The major problem with these inhibitors is that there is n
o simple way to compare their specificity and/or selectivity from one
report to another. We have set up a simple, straightforward technique
to compare the inhibitory potency of 14 classical inhibitors towards s
ix well-described and at least partially purified protein kinases. Thi
s technique is based on a new assay, easy to carry out and non-restric
tive in terms of the type of protein substrate used. It permits direct
comparisons between the results obtained from various sources. Data o
btained showed that, when assessed in this integrated system, specific
ity and selectivity of many ''classical'' inhibitors are often weak, t
hus demonstrating that a universal technique such as ours is essential
for the molecular screening of new protein kinase inhibitors. Compoun
ds showing specificity for this panel of protein kinases will be more
easily targeted to some defined types of oncogene and of transformed c
ells.