Journal: Frontiers in Bioengineering and Biotechnology

Article Title: A patent review of cyclin-dependent kinase 5 (CDK5) inhibitors (1999–2025)

doi: 10.3389/fbioe.2026.1843047

Figure Lengend Snippet: Structural basis of CDK5/p25 inhibition by pyrazole-based kinase inhibitors. (A) Close-up view of the ATP-binding pocket of the CDK5/p25 complex (chain A: red; chain D: blue) with Dinaciclib (cyan) bound. Key residues Leu83 and Asp86 (pink sticks) form hydrogen bonds (orange lines, distances in Å) with the inhibitor’s heterocyclic core and substituents. The surrounding protein surface is rendered semi-transparently in pink to highlight the binding cleft. (B) Global view of the CDK5/p25–Dinaciclib complex. Chain A (CDK5) is depicted as red ribbons, chain D (p25) as blue ribbons, and the molecular surface is shown in pink to delineate the active site region. Dinaciclib (cyan) occupies the canonical ATP-binding site between the N- and C-terminal lobes, consistent with its mechanism as a competitive ATP-mimetic inhibitor. (C) Chemical structures of representative pyrazole derivatives: Dinaciclib, Milciclib, PHA-793887, AT7519. 3D model created using SwissDock.

Article Snippet: PHA-793887 , Pyrazole derivative , CDK5, CDK2, CDK1 , ATP-competitive; nanomolar potency , Preclinical oncology studies ( ; Verastem, Inc., 2013; ) .

Techniques: Inhibition, Binding Assay