Fig. 4: CDK2 candidate selection and validation.
From: Optimizing drug design by merging generative AI with a physics-based active learning framework
A Scatter plot of CDK2 generated molecules with a Glide gscore below −8 kcal·mol−1 and a maximum similarity to the initial-specific set below 0.5. Red dotted lines indicate the stringent thresholds of −10 kcal·mol−1 for gscore and 0.3 for similarity used during the candidate selection. B Table with the MM affinity predictions and maximum similarity to the initial-specific set molecules for the synthesized molecules. C Structures of synthesized molecules. “A-“ denotes analog; (R) and (S) indicate right- and left-handed enantiomers, respectively. D Eight of the nine synthesized molecules presented in vitro activity against CDK2 with IC₅₀ values below 50 μM. Outer5_105 showed potent and complete inhibition of CDK2 with an IC50 of 71 nM. JNJ-770662197 was used as a control compound.
