Figure 1 from INX-315, a Selective CDK2 Inhibitor, Induces Cell Cycle Arrest and Senescence in Solid Tumors

Discovery and characterization of INX-315. A, Amino acid sequence homology at the ATP-binding pockets of several CDKs. B, Derivation of INX-315 through serial modifications of trilaciclib, a CDK4/6i. Table indicates biochemical IC₅₀s (± SEM) to cyclin/CDK pairings shown using the Nanosyn biochemical assay. Trilaciclib IC₅₀ for CDK1/cyclin B1 was ND (for trilaciclib: n = 6 for CDK2/cyclin E1 and CDK2/cyclin A2, n = 9 for CDK4/cyclin D1, n = 3 for other complexes; for compound B: n = 3 for all complexes; for compound C: n = 1 for all complexes; for INX-315: if SEM is 0, n = 1, otherwise n = 6). C, Modeling of INX-315 bound to cyclin E1/CDK2. D, NanoBRET assay quantifying INX-315's intracellular displacement of tracer from the ATP-pocket of the cyclin/CDK pairings shown. Table shows calculated IC₅₀s (two technical replicates per experiment, two biological replicates except for CDK2/Cyclin A1 where n = 1; error bars represent SD).BID, twice daily; QD, once daily.