APL-11056

APL-11056 (1 h) inhibits PERK-dependent eIF2α phosphorylation in U-2 OS cells with an IC₅₀ of 18 nM^[1].

APL-11056 (compound 49) (30 min) is a potent biochemical PERK inhibitor (IC₅₀ 1.63 nM; K_i 0.86 nM) with selectivity over GCN2, PKR, and HRI^[1].

APL-11056 (1 h) shows no measurable inhibition of GCN2 in U-2 OS cells and inhibits HRI-induced eIF2α phosphorylation only at 5738 nM^[1].

APL-11056 (10 µM) shows off-target activity against Lck and COX-1/COX-2 in the CEREP panel, with COX-1 IC₅₀ = 2.1 µM, and no COX-2 IC₅₀ is measured up to 10 µM^[1].

APL-11056 (2-20 µM; 2 h) exhibits high Caco-2 A-to-B permeability (4.91 × 10^-6 cm/s) with an efflux ratio as low as 6.7^[1].
APL-11056 (1 µM; 0-60 min) exhibits low intrinsic hepatic microsomal clearance (< 9.6 µL/min/mg) in the reported mouse, rat, and human liver microsome assays^[1].
APL-11056 (1 µM; 0-90 min) is metabolically stable in hepatocytes, with the lowest C_lint in dog (3.03) and human (5.10) and higher C_lint in rat (14.28) and mouse (17.42), in units of µL/min/10⁶ cells^[1].
APL-11056 shows no inhibition of CYP3A4-M, CYP2C9, CYP2D6, or CYP1A2 at concentrations up to > 20 µM^[1].
APL-11056 shows no inhibition of hERG up to > 30 µM in the dofetilide binding assay and patch-clamp assay^[1].
The intrinsic clearance of APL-11056 in human liver microsomes is 26.00 µL/min/mg, and its intrinsic clearance in rat liver microsomes is 20.13 µL/min/mg^[1].
The intrinsic clearance of APL-11056 in human hepatocytes is 5.095 µL/min/10⁶ cells, and the intrinsic clearance in rat and mouse hepatocytes is 9.32 µL/min/10⁶ cells^[1].
APL-11056 (10 µM) inhibits COX1 (91%), Lck (80%), and COX2 (64%) in the CEREP44 panel, with inhibition of most other targets ≤ 37%^[1].