Extended Data Fig. 5: Molecular docking, PK and toxicological data for Z218484536.
From: Pharmacological inhibition of PSPH reduces serine levels and epileptic seizures
(a) Docking score for the top 20 hits for PSPH inhibitors. (b) Binding mode and molecular interaction between Z218484536 and PSPH. (c) MST analysis of the binding of Z218484536 to PSPH. (d) In vivo PK data in mice after IP injection of a single dose of 4 mg/kg Z218484536. (e) PK profile of Z218484536 in the plasma and brain following a single IP administration of 4 mg/kg Z218484536 (n = 3 per time point). (f) Calculation of the brain/plasma ratio for Z218484536. (g, h) CCK-8 assays for Z218484536 (g) and LTG (h) in HepG2 cells. The cells were treated with each compound for 48 h before the CCK-8 assays were performed. (i) LD50 toxicity test for Z218484536. LD50 data are the averages from three independent experiments (n = 10 mice per group). (j-m) Performance of mice administered Z218484536 (4 mg/kg) or vehicle by IP injection for seven consecutive days in the open field test (j, k) and rotarod test (l, m) (n = 8 per group). (n, o) L-serine and glycine levels in the serum of mice administered Z218484536 (4 mg/kg, n = 6) or vehicle (n = 4) by IP injection for seven consecutive days. The data are shown as the means ± SDs or means with individual points. Statistical analysis was performed via two-tailed Student’s t test.
