Figure 6.

Allosteric MEK inhibitors induce sterility, embryonic lethality and vulva development phenotypes in C. elegans. 18 unique MEK inhibitors from the commercial libraries screened were included in our screen. These inhibitors were enriched for hits that induce the expected MEK-2 loss-of-function phenotypes including sterility (Ste) and the bag-of-worms phenotype (Bag), resulting from vulval induction defects preventing egg-laying (A-A′′, scale bar 0.1 mm). The resulting population growth defects are indicated by the colour coded scale (nb, no bacteria remaining in the well). (B) The allosteric inhibitor binding site of C. elegans MEK-2 (in blue) is well conserved with that of vertebrate MEK1 (in green, seen co-crystalized with allosteric inhibitor TAK-733 (PBD: 3PPI). The allosteric site contains only one amino acid difference, highlighted in pink (I99V).