FIGURE 1.

Computational pipeline and predicted drug-like properties for the discovery of AD-2441 and its analogs. (A) Oral CNS Scoring profile score vs logS of AD-2441 and its analogs, including two currently known control inhibitors, VY-3-249 and VY-3-135. Plot showing the StarDrop V7 (Optibrium, Ltd., Cambridge, United Kingdom)–derived logS versus a multimetric oral CNS profile score. Score composition and importance of each contributor: logS = 0.8, logP = 0.6, logD = 0.6, BBB category = 0.55, BBB log(brain:blood) = 0.55, P-gp category = 0.5, HIA = 0.4, hERG pIC50 = 0.2, 2D6 affinity category = 0.16, 2C9 pKi = 0.16, PPB90 category = 0.1. The size of the circle correlates with the corresponding score or probability. (B) Computational and SPR-based validation pipeline for the discovery of novel ACSS2 inhibitors.