Table 4. Profiles of Compounds 4 and 19–24.

^aPotency values are reported as arithmetic mean ± standard deviation from at least two independent experiments.

^bAll data were obtained using an enzymatic assay with purified kinase domain of ALK5 or TGF-βR2 in the presence of ATP at its K_m for each enzyme. Inhibition of enzymatic activity was measured using an ADP-Glo kit (Promega). The K_i values were calculated from IC₅₀ using the Cheng and Prusoff equation.

^cCellular pIC₅₀ values were obtained by measuring pSMAD2 levels in A549 cells stimulated for 1 h with 0.3 nM TGF-β1 with or without test compounds;

^dLipophilicity and pK_a were calculated using Chem Axon.

^eSolubility was evaluated from DMSO stock solutions by using HPLC UV.

^fIntrinsic permeability measured across Caco2 membranes; efflux ratio ER = (P_appBA)/(P_appAB).

^gHuman and mouse liver microsome intrinsic clearance (μL/min/mg prot).

^hPlasma protein binding (as fraction unbound %). *n.a.: no result available due to low recovery.

^IHuman/mouse and lung tissue binding (as fraction unbound %). *n.a.: no result available due to low recovery.