TABLE 2.

PD 184352 inhibition of directed MEK mutants as suggested by residues lining the putative binding pocket

MEK variantIC50 (μM)a ± range (n)Relative activity
Wild type0.067 ± 0.02 (2)1
Ile111Ala0.151 ± 0.01 (2)10
Ile111Asp>3 (2)4
Ile111Pro>1 (2)9
Ile111Arg>1 (2)4
Leu118Asp>3 (2)0.3
Leu118Pro>3 (2)0.13
Leu118Gly0.366 ± 0.05 (2)0.3
Leu118Gln>3 (2)0.5
Ile139Gly>3 (2)1
Ile139Arg0.143 (1)1
Ile139Asn0.247 (1)1
  • a Inhibition and the activities of MEK variants were measured against GSTERK(K71R) with various concentrations of PD 184352 in an in vitro kinase assay as described in Materials and Methods. Relative activities were normalized to the average basal activity of wild-type MEK from each experiment.