“Addition” and “Subtraction”: Selectivity Design for Type II Maternal Embryonic Leucine Zipper Kinase Inhibitors

While adding the
structural features that are
more favored by on-target activity is the more common strategy in
selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity
can also be very effective. Reported here is our successful effort
of improving the kinase selectivity of type II maternal embryonic
leucine zipper kinase inhibitors by applying these two complementary
approaches together, which clearly demonstrates the powerful synergy
between them.