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The pH-dependent solubility of the weakly basic TYK2 inhibitor posed a risk to its advancement, given that drugs with such profiles have exhibited drug-drug interaction (DDI) with stomach acid-reducing agents in humans. In a rat model of pH dependence, preadministration of famotidine caused a 2.4-fold lower exposure of when compared to control rats, implying that pH-dependent oral absorption can reduce the active drug's exposure and translate to subtherapeutic treatment.
View Article and Find Full Text PDFRebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive?
Int J Mol Sci
May 2024
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Landspitali University Hospital, 101 Reykjavik, Iceland.
Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production.
View Article and Find Full Text PDFVirtual drug repurposing study for the CGRPR identifies pentagastrin and leuprorelin as putative candidates.
J Mol Graph Model
November 2022
Computational Biology and Molecular Simulations Lab, Department of Biophysics, School of Medicine, Bahçeşehir University, İstanbul, Türkey; Bahçeşehir University, Graduate School, Neuroscience Program, İstanbul, Türkey. Electronic address:
Calcitonin gene-related peptide receptor (CGRPR) is a heterodimer consisting of CLR and RAMP1 proteins. Activation of the CGRPR with the endogenous peptide CGRP is known to play a crucial role in migraine pathophysiology. CGRP occupies two regions in the CGRPR upon binding, namely ectodomain and transmembrane sites (sites 1 and 2, respectively).
View Article and Find Full Text PDFCalcitonin: current concepts and differential diagnosis.
Ther Adv Endocrinol Metab
May 2022
5th Surgical Clinic, Department of Surgery, 'Evgenidion Hospital', National and Kapodistrian University of Athens Medical School, Athens, Greece.
Calcitonin (CT) is most effectively produced by the parafollicular cells of the thyroid gland. It acts through the calcitonin receptor (CTR), a seven-transmembrane class II G-protein-coupled receptor linked to multiple signal transduction pathways with its main secretagogues being calcium and gastrin. It is clinically used mostly in the diagnosis and follow-up of medullary thyroid carcinoma (MTC).
View Article and Find Full Text PDFIdentification of African Swine Fever Virus Inhibitors through High Performance Virtual Screening Using Machine Learning.
Int J Mol Sci
December 2021
Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54596, Korea.
African swine fever virus (ASFV) is a highly contagious virus that causes severe hemorrhagic viral disease resulting in high mortality in domestic and wild pigs, until few antiviral agents can inhibit ASFV infections. Thus, new anti-ASFV drugs need to be urgently identified. Recently, we identified pentagastrin as a potential antiviral drug against ASFVs using molecular docking and machine learning models.
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