Patent ID: 7792665

Claim:
A method for selecting a compound for modulating the activity of phosphoinositide dependent protein kinase 1 (PDK1), the method comprising: [i] generating a three-dimensional structure of the protein kinase catalytic domain of PDK1 as defined by Example 2, 3, 7 or 8; [ii] identifying predicted binding region(s): the PDK1 Interacting Fragment (PIF) binding pocket formed by residues including residues Lys115, Ile118, Ile119 on the αB helix, Val124, Val127 on the αC helix, and Leu 155 on β-sheet 5 of full length human PDK1 as set forth in SEQ ID NO: 3, the “phosphate binding pocket” formed by residues including residues Lys76, Arg131, Thr148 and Gln150 of full length human PDK1 as set forth in SEQ ID NO: 3, and/or the αC helix formed by residues 123-136 of full length human PDK1 as set forth in SEQ ID NO: 3 in any of the models generated in step [i]; [iii] modeling a plurality of three-dimensional structures of candidate compounds; [iv] comparing said three-dimensional structure of the protein kinase catalytic domain of PDK1 binding regions/pockets as identified in step [ii] with the three-dimensional structure of each of said candidate compounds of step [iii]; and [v] selecting one of the candidate compounds as a compound for modulating the activity of phosphoinositide dependent protein kinase 1 (PDK1).