Models for Predicting IKKA and IKKB Blockade

We describe the application of different methods in the
development
of QSAR models for IKKA and IKKB inhibition. The results show that
the best QSAR models provide highly accurate predictions for existing
IkB-kinase (IKK) inhibitors. The exceptions, corresponding to 5% of
the known collection of inhibitors, are five classes of compounds
incorporating the nitrile or sulfonamide moieties, small compounds
with molecular weights of less than 300, and two classes of blockers
considered to be type II kinase inhibitors. Comparison of our novel
IKKB homology model and the recently reported IKKB crystal structure
implies that a predictive protein–antagonist complex structure
is more likely to exist as an inactive form in the crystalline state
as observed in the recent protein X-ray structure.