Previously, our analysis of the Published Kinase Inhibitor Set (PKIS) revealed that VRK1 shared a similar activity profile to a small number of kinases, including members of the kinase family Ste20, such as MINK1 and TNIK. The Ste20 kinase family also includes MAP4K4, whose phosphate-binding loop (P-loop) can adopt an unusual conformation in which this conserved structural motif folds over the ligand. It has been suggested that this folded P-loop conformation might be targeted to obtain potent and selective kinase inhibitors. Co-crystal structures of VRK1 and VRK2 bound to the p90 RSK (ribosomal S6 kinase) inhibitor BI-D1870 (1 -Figure ) revealed that both kinases can also adopt the folded P-loop conformation, further suggesting that MAP4K4 and these two VRKs have similar topography and structural features in their binding sites. These observations motivated us to search for MAP4K4 chemical matter known to induce a folded P-loop conformation and that could be used as starting points to develop potent and selective inhibitors against VRK1 and VRK2.