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. 2023 Jun 3;14:3213. doi: 10.1038/s41467-023-38732-x

Fig. 1. Binding characterization of anthranilic acids as CDK2 allosteric inhibitors.

Fig. 1

a Cocrystal structure of 1 (yellow) bound to an allosteric pocket of CDK2 (PDB ID 7RWF). The C-helix is shown in magenta, the activation loop in blue, the DFG motif in green, the hinge region in orange, and the gatekeeper residue F80 in red. b Surface presentation of the compound 1-CDK2 complex in two orientations. Compound 1 is buried and largely shielded from solvent. c Detailed view of the binding site and interacting residues. H-bonds (d = 2.2–3.5 Å) are indicated as black dotted lines. Hydrophobic van-der-Waals interactions (d = 3.3–4.0 Å) were omitted for clarity. d Chemical structures of CDK2 allosteric inhibitors. e ITC traces and thermodynamic binding values of 1 (left) and 5 (right). f One of two independent SPR replicates in Supplementary Fig. 3. g Cocrystal structure of CDK2 with compound 1 and dinaciclib (pink, PDB ID 8FOW). h Cocrystal structure of CDK2 with compound 1 and roscovitine (pink, PDB ID 8FP0). g and h Demonstrate the noncompetitive, allosteric nature of compound 1.