Mean docking scores were: −8.34 kcal/mol (CK1δ), −8.80 kcal/mol (PINK1), −7.56 kcal/mol (SMO), and −6.76 kcal/mol (TIE2), with highly significant preferential binding to developmental kinases versus the control ( p < 0.001 for all comparisons).
The marginally non-significant trend for PINK1 ( p = 0.056)—the largest observed between-class difference (1.11 kcal/mol), with upstream SMO-targeting compounds showing somewhat stronger PINK1 engagement than downstream modulators—may reflect the structural features of SMO-binding scaffolds (morpholine rings, purine cores, aromatic amides) that are geometrically compatible with the PINK1 ATP-binding pocket, though this interpretation requires experimental biochemical confirmation.
Critically, between-class comparisons—testing whether upstream and downstream compounds differ in their affinity for each individual target—did not reach statistical significance for any target (CK1δ: p = 0.497, ns; PINK1: p = 0.056, ns; SMO: p = 0.380, ns; TIE2: p = 0.748, ns), consistent with the reduced sample sizes in each subgroup (n = 9 and n = 8) relative to the full 17-compound panel analyzed in Figure 6 B.