tenatoprazole (sTU-199) / Mitsubishi Tanabe - LARVOL DELTA

β-Coronaviruses exploit ESCRT for virion assembly and egress. (PubMed, mBio) - "Downregulation of these ESCRT factors or VPS4A, or treatment of cells with the TSG101 antagonist tenatoprazole significantly inhibited the production of the virion-like particles of β-coronaviruses and the replication of human coronavirus OC43...Treatment of cells with the TSG101 antagonist inhibited the assembly of multiple β-coronaviruses. These findings indicate that ESCRT participates in β-coronavirus assembly and egress and might be a potential target for the development of broad-spectrum anti-coronavirus therapeutics."

Journal • Infectious Disease • Novel Coronavirus Disease • TSG101

Preparation and study of a capillary electrochromatographic column prepared by conjugating β-CD COFs and gold-poly glycidyl methacrylate nanoparticles. (PubMed, Mikrochim Acta) - "The performance of the fabricated capillary column was evaluated by CEC using enantiomers of seven model analytes, including two proton pump inhibitors (PPIs, omeprazole and tenatoprazole), three amino acids (AAs, tyrosine, phenylalanine, and tryptophan), and two fluoroquinolones (FQs, gatifloxacin and sparfloxacin). Furthermore, molecular docking studies were performed based on the chiral fabricated column and as ligand isomers of analytes using Auto Dock Tools. The binding energies and interactions acquired from docking results of analytes supported the experimental data."

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Acid-suppressive drugs: A systematic review and network meta-analysis of their nocturnal acid-inhibitory effect. (PubMed, Pharmacotherapy) - "This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs."

Journal • Retrospective data • Review

Development of an assay pipeline for the discovery of novel small molecule inhibitors of human glutathione peroxidases GPX1 and GPX4. (PubMed, Redox Biol) - "Additionally, every GPX1 inhibitor identified (including omapatrilat, tenatoprazole, cefoxitin and ceftibuten) showed similar inhibitory activity against GPX2...Compounds only inhibiting GPX4 included pranlukast sodium hydrate, lusutrombopag, brilanestrant, simeprevir, grazoprevir (MK-5172), paritaprevir, navitoclax, venetoclax and VU0661013. Two compounds (metamizole sodium and isoniazid sodium methanesulfate) inhibited all three GPXs but not TXNRD1, while 2,3-dimercaptopropanesulfonate, PI4KIII beta inhibitor 3, SCE-2174 and cefotetan sodium inhibited all tested selenoproteins (but not GR)...With this approach, we could indeed identify novel GPX1/GPX2- or GPX4-specific inhibitors, thus presenting a validated pipeline for future identification of specific selenoprotein-targeting agents. Our study also identified GPX1/GPX2, GPX4 and/or TXNRD1 as targets for several previously developed pharmacologically active compounds."

Journal • Oncology • GPX1 • GPX2 • GPX4

Preparation of β-cyclodextrin covalent organic framework-immobilized poly(glycidyl methacrylate) nanoparticle-coated open tubular capillary electrochromatography column for chiral separation. (PubMed, J Sep Sci) - "The chiral separation performance of the fabricated capillary columns was validated by the analysis of the four racemic proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, and omeprazole. In the optimum conditions, the enantiomers of four proton pump inhibitors were fully resolved within 10 min with high resolutions of 9.5-13.9. The column-to-column and inter- to intra-day repeatability of the fabricated capillary columns through relative standard deviation were found better than 9.54%, exhibiting satisfactory stability and repeatability of the fabricated capillary columns."

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Roles of Human Liver Cytochrome P450 Enzymes in Tenatoprazole Metabolism. (PubMed, Pharmaceutics) - "Furthermore, a new major metabolite of tenatoprazole sulfide was found, 1'-N-oxy-5'-hydroxytenatoprzole sulfide, which has never been reported. In conclusion, the metabolic fates of tenatoprazole and tenatoprazole sulfide should be considered in the clinical use of tenatoprazole."

Journal • Gastrointestinal Disorder • Peptic Ulcer • CYP2C19 • CYP3A4

β-Cyclodextrin Covalent Organic Framework supported by polydopamine as stationary phases for electrochromatographic enantioseparation. (PubMed, Electrophoresis) - "Furthermore, the chiral separation effectiveness of the fabricated capillary column was evaluated by capillary electrochromatography using enantiomers of several related proton pump inhibitors as model analytes, including omeprazole, lansoprazole, pantoprazole and tenatoprazole. The relative standard deviation values for migration times and resolutions of the analytes representing intraday and interday were less than 6.75 and 4.24%, respectively. The results reveal that ?-cyclodextrin covalent organic framework has great potential as chiral stationary phases for enantioseparation in capillary electrochromatography."

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Preparation of a polydopamine/β-cyclodextrin coated open tubular capillary electrochromatography column and application for enantioseparation of five proton pump inhibitors. (PubMed, J Sep Sci) - "The prepared columns showed good chiral separation performance towards five proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, rabeprazole and omeprazole. The relative standard deviation values for migration times and peak areas of the analytes representing intra-day and inter-day were less than 1.9 and 3.6 %, respectively. Further, the polydopamine/?-cyclodextrin coated capillary column could be successively used over 100 runs without showing significant decrease in the separation efficiency."

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Chiral separation in the class of proton pump inhibitors by chromatographic and electromigration techniques: An overview. (PubMed, Electrophoresis) - "Moreover, two representatives of the class are used in therapy both as racemates and as pure enantiomers (esomeprazole, dexlansoprazole)...Analytical and bioanalytical methods using different chromatographic and electromigration techniques reported for the enantioseparation of omeprazole, lansoprazole, pantoprazole, rabeprazole, ilaprazole, and tenatoprazole are included...Color online: See article online to view Figs. 1 and 7 in color."

Journal • Review

Electrophilic and Drug-Induced Stimulation of NOTCH3 N-terminal Fragment Oligomerization in Cerebrovascular Pathology. (PubMed, Transl Stroke Res) - "Electrophilic clinical drugs (fenoldopam, omeprazole, tenatoprazole, lansoprazole, and rabeprazole) also promoted oligomerization, and we identified direct omeprazole-NTF and tenatoprazole-NTF complexes. A broad array of electrophilic chemicals, including clinically relevant drugs, influences oligomerization of a pathological CADASIL protein, providing mechanistic insight into disease protein oligomerization. We posit that environmental influences, which may include usage of electrophilic drugs, may affect CADASIL presentations."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • NOTCH3

Ilaprazole and other novel prazole-based compounds that bind Tsg101 inhibit viral budding of HSV-1/2 and HIV from cells. (PubMed, J Virol) - "Ilaprazole also quantitatively blocks the release of HIV-1 from 293T cells with an EC of 0.8-1.2 μM, which is much more potent than tenatoprazole. Our results indicate that prazole-based compounds may represent a class of drugs with potential to be broad-spectrum antiviral agents against multiple enveloped viruses, by interrupting cellular Tsg101 interaction with maturing virus, thus blocking the budding process that releases particles from the cell.ImportanceThese results provide the basis for the development of drugs that target enveloped virus budding that can be used ultimately to control multiple virus infections in humans."

Journal • Herpes Simplex • Human Immunodeficiency Virus • Infectious Disease

Effectiveness and safety of proton pump inhibitors for treating acute pancreatitis: A protocol for systematic review and meta analysis. (PubMed, Medicine (Baltimore)) - "This study will provide reliable evidence-based evidence for the clinical application of PPIs for treating AP."

Journal • Retrospective data • Review • Pancreatitis

The giardicidal activity of lobendazole, fabomotizole, tenatoprazole and ipriflavone: A ligand-based virtual screening and in vitro study. (PubMed, Eur J Med Chem) - "Particularly, tenatoprazole showed the best effect against the WB and IMSS strains. Furthermore, fabomotizole, tenatoprazole and ipriflavone showed a higher activity against resistant strains than the reference drugs: metronidazole, albendazole and nitazoxanide."

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Selective Targeting of Virus Replication by Proton Pump Inhibitors. (PubMed, Sci Rep) - "Two proton pump inhibitors, tenatoprazole and esomeprazole, were previously shown to inhibit HIV-1 egress by blocking the interaction between Tsg101, a member of the ESCRT-I complex, and ubiquitin. Another key finding is that prazole prodrugs must be activated inside the cell, while their rate of activation in vitro correlated to their efficacy in cells. Our study lays the groundwork for future efforts to repurpose prazole-based compounds as antivirals that are both broad-spectrum and selective in nature."

Journal • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation

Binding of omeprazole to protein targets identified by monoclonal antibodies. (PubMed, PLoS One) - "At least two other clinically used PPIs, rabeprazole and tenatoprazole, are capable of binding to proteins in a similar fashion. We conclude that omeprazole binds to multiple proteins and is capable of forming highly stable complexes that are not dependent on disulfide linkages between the drug and protein targets. Further studies made possible by these antibodies may shed light on whether PPI-protein complexes underlie off-target untoward effects of chronic PPI use."

Journal • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Peptic Ulcer

Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex. (PubMed, ACS Chem Biol) - "Here we report the identification of adipoylphosphonic acid and tenatoprazole as DHTKD1 inhibitors using targeted and high throughput screening, respectively...Whereas the majority of the DHTKD1 variants displayed impaired folding or reduced thermal stability in combination with absent or reduced enzyme activity, three variants showed no abnormalities. Our work provides chemical and structural tools for further understanding of the function of DHTKD1 and its role in several human pathologies."

Journal • Eosinophilic Esophagitis • Genetic Disorders

Influence of organic modifier and separation modes for lipophilicity assessment of drugs using thin layer chromatography indices. (PubMed, J Chromatogr A) - "In the present work thin layer chromatography (TLC) has been utilized to evaluate lipophilicity of 11 representative drugs, which included six proton pump inhibitors (omeprazole, pantoprazole, rabeprazole, lansoprazole, ilaprazole, and tenatoprazole), an anti-vertigo drug, betahistine, nonsteroidal anti-inflammatory drug, ibuprofen, anti-malarial drug, atovaquone, an anti-HIV agent, atazanavir and a hormonal drug, calcitriol. Principal component analysis, hierarchical cluster analysis, as well as non-parametric methods like sum of ranking differences and generalized pair wise correlation revealed the dominant pattern in the data. The results obtained from both the separation modes were comparable and were in good agreement with the computational data for all the drugs."

Journal • Biosimilar • Gene Therapies

ASSESSMENT OF THE KYNURENINE PATHWAY OF TRYPTOPHAN METABOLISM IN PRIMARY BRAIN TUMORS (SNO 2017) - "Primary patient-derived cell cultures were treated with commercially available small molecule inhibitors for IDO1 (epacadostat), IDO2 (tenatoprazole), TDO2 (680C91), and AhR (CH-223191). These results suggest that inhibition of AhR, and not the rate-limiting enzymes of the KP, may offer a novel therapeutic target for a patient population with highly limited treatment options."

Solid Tumor

Proton pump inhibitors act with unprecedented potencies as inhibitors of the acetylcholine biosynthesizing enzyme-A plausible missing link for their association with incidence of dementia. (PubMed, Alzheimers Dement) - "Given that accumulating evidence points at cholinergic dysfunction as a driving force of major dementia disorders, our findings mechanistically explain how prolonged use of PPIs may increase incidence of dementia. This call for restrictions for prolonged use of PPIs in elderly, and in patients with dementia or amyotrophic lateral sclerosis."

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Determination of Proton Pump Inhibitors by Spectrophotometric, Chromatographic and by Hyphenated Techniques: A Review. (PubMed, Crit Rev Anal Chem) - "The review includes literature survey of PPI drugs namely omeprazole (OPZ), lansoprazole (LPZ), pantoprazole (PPZ) rabeprazole (RPZ), dexlansoprazole (DLPZ), esomeprazole (EPZ), dexrabeprazole (DRPZ), ilaprazole (IPZ), and tenatoprazole (TPZ). The examined literature survey addressed chromatographic (HPLC and UPLC) and UV visible spectrophotometric methods with LC-MS/MS methods used in pure forms, pharmaceutical formulations, and human plasma and other biological fluids for their estimation. In case of validation parameters mostly Linearity, Recovery study, LOD and LOQ was considered and mentioned."

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