Omeprazole

Omeprazole (H 16868) is an orally active H⁺,K⁺-ATPase inhibitor and a proton pump inhibitor. Omeprazole competitively inhibits CYP2C19, CYP3A4, and CYP2C9 activity. Omeprazole inhibits gastric acid secretion and can be used for acid-related gastrointestinal disorders. Omeprazole inhibits pancreatic cancer cell proliferation, induces apoptosis, autophagosome accumulation (elevated LC3-I and LC3-II levels), oxidative stress, and cytogenetic imbalance, modulates lysosomal transport, reduces inflammatory cytokines. Omeprazole alters small intestinal morphology and magnesium absorption, and induces gastric mucosa morphologic changes. Omeprazole aslo has neuroprotective and antibacterial effects^{[1][2][3][4][5]}. IC50 & Target:Proton Pump^[1] In Vitro:Omeprazole (15 min) competitively inhibits CYP2C9 activity in pooled human liver microsomes with a K_i of 16.4 μM^[1].
Omeprazole (20 min) competitively inhibits CYP2C19 activity in pooled human liver microsomes with a K_i of 2.4-6.2 μM μM^[1].
Omeprazole (15 min) does not significantly inhibit CYP2D6 activity in pooled human liver microsomes, with an IC₅₀ >200 μM^[1].
Omeprazole (15 min) competitively inhibits CYP3A4 activity in pooled human liver microsomes with a K_i of 41.9 μM^[1].
Omeprazole (0-200 μg/mL; 4 days) inhibits proliferation of MiaPaCa-2, ASPC-1, Panc-1, Colo357, PancTu-1, and Panc89 human pancreatic cancer cell lines in a dose-dependent manner with IC₅₀ values ranging from 9.1 to 42.4 μg/mL^[2].
Omeprazole (80 μg/mL; 30 min-24 ) does not cause consistent intralysosomal pH changes in MiaPaCa-2 and ASPC-1 human pancreatic cancer cell lines, but increases acidity in ASPC-1 cells and decreases acidity in MiaPaCa-2 cells after 24 hours of incubation at 80 μg/mL^[2].
Omeprazole (80-160 μg/mL; 24 h) induces accumulation of early autophagic markers (phagophores and autophagosomes) in MiaPaCa-2 and ASPC-1 human pancreatic cancer cell lines, and induces apoptosis in ASPC-1 cells^[2].
Omeprazole (80 μg/mL; 24 h) accumulates intracellularly in MiaPaCa-2 and ASPC-1 human pancreatic cancer cell lines, and induces changes in fatty acid and phospholipid metabolism^[2].
Omeprazole (80 μg/mL; 24 h) alters the distribution of lysosomal markers and reduces Golgi complex marker expression in MiaPaCa-2 human pancreatic cancer cells, indicating disruption of the lysosomal transport pathway without accumulating in lysosomes or the Golgi complex^[2].
Omeprazole (40-160 μg/mL; 24 h) induces autophagy in a dose-dependent manner with elevated LC3-I and LC3-II levels, and impairs autophagosome turnover in MiaPaCa-2 and ASPC-1 human pancreatic cancer cell lines^[2].
Omeprazole (80 μg/mL; 6-24 h) alters gene expression in ASPC-1 and MiaPaCa-2 human pancreatic cancer cell lines, downregulating bad and survivin and upregulating mdr-1 in ASPC-1 cells^[2].
Omeprazole (80 μg/mL; 24 h) activates autophagy via upregulation of Atg12 in MiaPaCa-2 and ASPC-1 human pancreatic cancer cell lines, and upregulates pro-apoptotic Puma in ASPC-1 cells^[2].
Omeprazole generate sulfone, sulfite
and hydroxy-omeprazole, compounds that can generate more oxidative damage ^[3].
Omeprazole exerts toxicogenic effects in Allium cepa plant cells, as well as Saccharomyces cerevisiae and murine Sarcoma 180 cells^[3].
Omeprazole (200-300 mg/L) results in a
dose-dependent inhibition of E.faecalis at time zero^[6].
Omeprazole (200 mg/L) inhibits S. aureus at both time zero and 2 h^[6]. In Vivo:Omeprazole (20 mg/kg; s.c.; daily; 12-24 weeks) in male Sprague-Dawley rats induces small intestinal inflammation, villous atrophy, tight junction narrowing, and systemic magnesium deficiency with hypomagnesemia^[4].
Omeprazole prevents Oxaliplatin (HY-17371)-induced peripheral neuropathy in Rattus norvegicus^[5].
Omeprazole reduces the levels of the inflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6, in sciatic nerve-ligated mice^[5].