Fig. 4. Summary of PI3Kα allosteric inhibitor pockets. (A) The full structure of PI3Kα with the allosteric pocket highlighted. The allosteric pocket for PIK-108 (PIK in the figure) is identified from the crystal structure of PI3Kα (PDB ID 4A55), the allosteric pockets F1–F5 are obtained from fragment-based screening27 and the allosteric pocket between ABD and kinase domain (AD in the figure) is proposed in the work. (B) The snapshot of PIK-108 interacting with a non-APT pocket in the C-lobe of kinase domain. The ATP is modeled based on the PI3K structure (PDB ID ; 1E8X). (C) The snapshot of the proposed allosteric pocket between ABD and N-lobe kinase domain.
