Based on the available information, it appears that the ability to H bond may be crucial for inhibitory effect at TBK1. Consequently, structural features capable of H bonding (donors and acceptors) are likely important. Also, inhibitors having variations of the purine moiety are likely to be effective since inhibitors have to compete with ATP for the binding site. Structural elements capable of engaging in Van der Waals interactions with hydrophobic residues likely help boost inhibitory potency. Finally, structural elements that aid in pushing the gatekeeper residue Met 86, such as bulky substituents (5 or 6 membered rings) are likely to also increase inhibitory potency.