Dr.Reddy's Laboratories Ltd. · ATP4A · 小分子
omeprazole 是一种小分子，由Dr.Reddy's Laboratories Ltd.研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。
| 商品名 | Omez Insta |
| 公司 | Dr.Reddy's Laboratories Ltd. |
| 药物类别 | 小分子 |
| 分子靶点 | ATP4A |
| 给药途径 | Oral (PO) |
| 状态 | Approved |
omeprazole 作用于 1 个分子靶点：
| ATP4A | ATPase H+/K+ transporting subunit alpha (ATP6A) |
omeprazole 针对 1 个适应症，涉及 1 个治疗领域。
| 治疗领域 | 疾病/病症 | 分期 |
|---|---|---|
| Gastrointestinal disorders | Gastritis | ✓ Approved |
Xue Fangwei F, Zhao Shengran S, Han Peilin P
Pasookhush Phongthana P, Suta Sophida S, Pumeiam Sureeporn S, Mongkolsucharitkul Pichanun P et al.
Pharmacogenomic (PGx) data in Thailand remain limited, and genetics-only surveys rarely quantify "realized actionability"-the overlap between actionable PGx phenotypes and real-world medication exposure. We profiled 4,662 Thai adults using SNP-array data and a pre-specified PGx panel (11 genes; 26 markers) with a hybrid required/optional calling policy for diplotype/phenotype assignment. CPIC level A/B gene-drug relationships were linked to hospital electronic medical record (EMR) prescription/dispensation data to quantify drug-specific realized actionability. Overall callability across gene-results was 98.62%, exceeding 99% for most genes and lower for CYP2C19 (95.99%) and NUDT15 (90.28%). Across nine phenotype-coded genes, 95.99% carried ≥1 CPIC-actionable result (median 2; IQR 2-3). Actionable prevalence among callable individuals was highest for CYP3A5 (58.54%) and CYP2C19 (56.67%), followed by ABCG2 (45.10%) and UGT1A1 (27.37%). EMR linkage identified 1,529 (32.58%) participants exposed to ≥1 study medication; omeprazole (n = 658) and statins were most common (atorvastatin n = 606; simvastatin n = 603). Among users, actionable phenotypes were frequent for CYP2C19-omeprazole (55.02%) and SLCO1B1-statins (21.95-23.05%). In conclusion, an Asian-optimized SNP array supports scalable PGx phenotyping in Thai adults. EMR linkage quantifies realized actionability and highlights high-yield targets (CYP2C19-proton pump inhibitors; SLCO1B1-statins) for pre-emptive implementation.
Ding Hai-Yan HY, Gou Hai-Ying HY, Meng Jin-Ni JN, You Qiang Q et al.
This study investigated the differences in protective effects of aqueous extracts from stone-epiphytic and living tree-epiphytic Dendrobium nobile on alcohol-induced gastric ulcers in rats, and elucidated the scientific connotation of the traditional assertion that "Dendrobium grown on stones is superior" from the perspectives of material basis and pharmacodynamics. The chemical profiles of aqueous extracts from the two cultivation modes were compared. Rats were randomly divided into control group, model group, omeprazole group, low-and high-dose stone-epiphytic D. nobile(LSE, HSE) groups, and low-and high-dose living tree-epiphytic D. nobile(LLT, HLT) groups. An acute gastric ulcer model in SD rats was established by intragastric administration of absolute ethanol. Gastric mucosal injury index, ulcer inhibition rate, and gastric juice pH were determined. Histopathological changes in gastric tissue were observed by hematoxylin-eosin(HE) and Alcian blue-periodic acid-Schiff(AB-PAS) staining. The expression of tight junction proteins zonula occludens-1(ZO-1) and occludin was detected by immunohistochemistry. Levels of oxidative stress markers, including malondialdehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO), as well as interleukin-6(IL-6), interleukin-1β(IL-1β), and interferon-γ(IFN-γ) in serum and gastric tissue were measured. Non-targeted metabolomics was further employed to identify absorbed constituents in serum, screen differential metabolites, and perform pathway enrichment analysis, thereby systematically evaluating the material basis and pharmacodynamic differences between the two cultivation modes of D. nobile. The results showed that the aqueous extracts from both cultivation modes contained largely similar types of chemical constituents, including flavonoids, alkaloids, terpenoids and terpenoid glycosides, glycosides, and phenolic amides. However, the relative contents of alkaloid and terpenoid components in both aqueous extracts and absorbed serum samples were higher in stone-epiphytic D. nobile than in living tree-epiphytic samples. Compared with the model group, gastric mucosal injury was significantly alleviated in all treatment groups, with the HSE group showing the highest ulcer inhibition rate. Histopathological observations further indicated that HSE was superior to HLT in maintaining gastric mucosal structural integrity and promoting mucus secretion. Compared with the model group, HSE significantly upregulated the expression of ZO-1 and occludin, effectively reduced MDA and NO levels, and increased SOD activity in gastric tissue, while decreasing the levels of IL-6, IL-1β, and IFN-γ in serum and gastric tissue. Serum metabolomics analysis further showed that HSE mainly exerted protective effects by regulating glycerophospholipid metabolism and glycosylphosphatidylinositol(GPI)-anchor biosynthesis pathways, whereas HLT mainly affected primary bile acid biosynthesis and lysine degradation pathways. These results indicate that both stone-epiphytic and living tree-epiphytic D. nobile exert protective effects against alcohol-induced gastric ulcers. However, the efficacy of stone-epiphytic D. nobile is significantly superior. This advantage may be closely related to the higher relative contents of alkaloid and terpenoid components in both aqueous extracts and absorbed serum samples, as well as its stronger antioxidant and anti-inflammatory activities, better protection of gastric mucosal barrier integrity, and more pronounced regulation of specific metabolic pathways. These findings provide modern pharmacodynamic evidence for the traditional assertion that "Dendrobium grown on stones is superior".
Wu Tung-Yun TY, Chen Che-Yi CY, Chen Michael M, Wang Chang-Hung CH et al.
Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of pancreatic β cells. Current insulin therapy does not address autoimmune pathology or restore endogenous β-cell function, highlighting the need for disease-modifying strategies. We developed a combination therapy integrating a proton pump inhibitor (PPI; omeprazole) with a non-Fc-binding anti-CD3 F(ab')2 antibody fragment (anti-CD3 F(ab')2) to concurrently promote β-cell neogenesis and modulate autoimmune T-cell responses. T1D was induced in nonobese diabetic (NOD) mice using a cyclophosphamide-accelerated protocol (CY-NOD). Following hyperglycemia onset, mice received combination treatment and were evaluated by blood glucose monitoring, flow cytometric analysis of T-cell populations, and assessment of pancreatic β-cell function. Therapeutic efficacy was further examined in spontaneous-onset NOD mice. Combination therapy restored normoglycemia without exogenous insulin, reduced lymphocytic infiltration in pancreatic islets, and preserved endogenous insulin secretion. Treatment decreased pathogenic CD4+ and CD8+ T cells, increased regulatory T cells, and enhanced transforming growth factor-β expression. Comparable and durable glycemic control was observed in spontaneous-onset NOD mice. Concurrent modulation of β-cell function and autoimmune immunity achieved sustained glycemic control in T1D models. The use of clinically approved agents supports the translational potential of this non-insulin-dependent therapeutic strategy.
Uno Yasuhiro Y, Fukunaga Koya K, Yamazaki Hiroshi H
Drug oxygenation is primarily carried out by cytochromes P450 (P450s, CYPs) and by flavin-containing monooxygenases (FMOs). Genetic variations of P450s and FMOs significantly contribute to differences in drug metabolism among individuals and populations. Moreover, species-specific differences in drug metabolism pose challenges during drug discovery and development. Dogs and pigs are commonly used as animal models in preclinical drug development studies. Consequently, this mini-review updates and summarizes the data from dogs and pigs used as models for predicting and comparing human drug metabolism. This research update presents the most recent findings on genetic variants of P450 and FMO enzymes in dogs and pigs and makes comparisons with their human counterparts. Recently, genetic variants of dog CYP2B6 and CYP2C21 have been identified and analyzed. In dog CYP2B6, the V103I, Q233L, and R145Q variants exhibited reduced propofol oxidation activities compared to the wild type, whereas a splice variant resulting in E275del demonstrated increased metabolic activity. In dog CYP2C21, the R125C variant showed diminished omeprazole oxidation activity relative to the wild type, and a frameshift variant (c.669dupA) led to a truncated protein, rendering it a null allele. Furthermore, liver microsomes from minipigs with CYP1A2 variant F260L showed reduced caffeine C8-hydroxylation activity compared to the wild type. Additional information on other P450s and FMOs is included. The summarized information enhances our understanding of individual pharmacokinetic and toxicological outcomes in dogs and pigs used as preclinical models and illuminates the molecular mechanisms of P450 and FMO functionality in humans.
Cesur Selcan S, Yalinbas-Kaya Berrin B
Background/Objectives: Spinosin, a flavone glycoside derived from medicinal plants, has been widely studied for its neuroactive properties; however, its effects on gastric injury remain unclear. Therefore, this study investigated the potential protective role of spinosin against HCl/ethanol-induced gastric lesions and its association with Nrf2/HO-1-related antioxidant responses. Methods: Gastric ulceration was experimentally induced in male Swiss albino mice by intragastric administration of 0.3 M HCl in 70% ethanol. Spinosin was administered orally at doses of 10 and 20 mg/kg, while omeprazole (20 mg/kg) was used as a reference treatment. Results: HCl/ethanol exposure led to pronounced oxidative stress and inflammatory responses, as reflected by increased levels of MDA, NFκB, IL-6, TNF-α, Cox-2, iNOS, IL-1β, Bax, and Cas-3, along with reduced antioxidant enzyme activities (GSH, SOD, CAT), decreased PGE2 and NO levels, and downregulation of Nrf2, HO-1, and Bcl-2 expression. Spinosin administration significantly attenuated gastric injury, suppressed pro-inflammatory mediators, reduced markers of lipid peroxidation and apoptosis, and enhanced antioxidant defenses. In parallel, spinosin treatment was associated with increased expression of Nrf2, HO-1, and Bcl-2. Conclusions: These findings suggest that spinosin mitigates gastric damage and is associated with attenuation of oxidative stress, inflammatory responses, and apoptosis, suggesting a possible contribution of Nrf2/HO-1-related antioxidant responses.
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