Delving into the Latest Updates on Lavoltidine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Loxtidine

+ [2]

Target

H2 receptor x TBXA2R

Action

antagonists

Mechanism

H2 receptor antagonists(Histamine H2 receptor antagonists), TBXA2R antagonists(Thromboxane A2 receptor antagonists)

Therapeutic Areas

Digestive System DisordersMouth and Tooth DiseasesOtorhinolaryngologic Diseases+ [1]

Active Indication-

Inactive Indication

Gastroesophageal RefluxHeartburn

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC19H29N5O2

InChIKeyVTLNPNNUIJHJQB-UHFFFAOYSA-N

CAS Registry76956-02-0

Current treatment for gastroesophageal reflux disease(GERD)confirms an unmet need in patients, based on slow onset of action and an inability to provide 24-hour gastric acid suppression. Clinical data on lavoltidine demonstrates a rapid onset of action, high potency, and prolonged duration of effect after single dose. Since tolerance to the class of compounds to which lavoltidine belongs may be dose dependent, the current study is designed to determine if 40mg lavoltdine given for 7days develops tolerance.

Start Date01 May 2007

Sponsor / Collaborator

GSK Plc

NCT00405119

/ CompletedPhase 2

A Randomized, Double-blind, Four Period Cross-over Comparison of the Effect of Two Doses Lavoltidine, Esomeprazole, and Placebo on 24 Hour Gastric pH and Frequency of Heartburn in Symptomatic GERD Subjects Without Esophageal Erosions

Current treatment for gastroesophageal reflux disease (GERD) confirms an unmet need in patients, based on slow onset of action and an inability to provide 24-hour gastric-acid suppression. Clinical data on AH234844 demonstrates a rapid onset of action, high potency, and prolonged duration of effect. The present study endeavors, in part, to compare lavoltidine to two GERD drugs, NEXIUM and ranitidine.

Start Date01 May 2006

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with Lavoltidine

Login to view more data

100 Translational Medicine associated with Lavoltidine

Login to view more data

100 Patents (Medical) associated with Lavoltidine

Login to view more data

65

Literatures (Medical) associated with Lavoltidine

01 Sep 2015·Toxicological SciencesQ2 · MEDICINE

Toxicokinetic Triage for Environmental Chemicals

Q2 · MEDICINE

Article

Author: Sluka, James P ; Tropsha, Alex ; Thomas, Russell S ; Bosgra, Sieto ; Goldsmith, Rocky ; Setzer, R Woodrow ; Wetmore, Barbara A ; Judson, Richard ; Sedykh, Alexander ; Strope, Cory ; Shah, Imran ; Pearce, Robert ; Wambaugh, John F

Toxicokinetic (TK) models link administered doses to plasma, blood, and tissue concentrations. High-throughput TK (HTTK) performs in vitro to in vivo extrapolation to predict TK from rapid in vitro measurements and chemical structure-based properties. A significant toxicological application of HTTK has been "reverse dosimetry," in which bioactive concentrations from in vitro screening studies are converted into in vivo doses (mg/kg BW/day). These doses are predicted to produce steady-state plasma concentrations that are equivalent to in vitro bioactive concentrations. In this study, we evaluate the impact of the approximations and assumptions necessary for reverse dosimetry and develop methods to determine whether HTTK tools are appropriate or may lead to false conclusions for a particular chemical. Based on literature in vivo data for 87 chemicals, we identified specific properties (eg, in vitro HTTK data, physico-chemical descriptors, and predicted transporter affinities) that correlate with poor HTTK predictive ability. For 271 chemicals we developed a generic HT physiologically based TK (HTPBTK) model that predicts non-steady-state chemical concentration time-courses for a variety of exposure scenarios. We used this HTPBTK model to find that assumptions previously used for reverse dosimetry are usually appropriate, except most notably for highly bioaccumulative compounds. For the thousands of man-made chemicals in the environment that currently have no TK data, we propose a 4-element framework for chemical TK triage that can group chemicals into 7 different categories associated with varying levels of confidence in HTTK predictions. For 349 chemicals with literature HTTK data, we differentiated those chemicals for which HTTK approaches are likely to be sufficient, from those that may require additional data.

20 May 2013·Chemical Research in ToxicologyQ3 · MEDICINE

Carcinogenicity Prediction of Noncongeneric Chemicals by a Support Vector Machine

Q3 · MEDICINE

Article

Author: Nie, Xianglei ; Zhong, Min ; Yan, Aixia ; Yuan, Qipeng

The ability to identify carcinogenic compounds is of fundamental importance to the safe application of chemicals. In this study, we generated an array of in silico models allowing the classification of compounds into carcinogenic and noncarcinogenic agents based on a data set of 852 noncongeneric chemicals collected from the Carcinogenic Potency Database (CPDBAS). Twenty-four molecular descriptors were selected by Pearson correlation, F-score, and stepwise regression analysis. These descriptors cover a range of physicochemical properties, including electrophilicity, geometry, molecular weight, size, and solubility. The descriptor mutagenic showed the highest correlation coefficient with carcinogenicity. On the basis of these descriptors, a support vector machine-based (SVM) classification model was developed and fine-tuned by a 10-fold cross-validation approach. Both the SVM model (Model A1) and the best model from the 10-fold cross-validation (Model B3) runs gave good results on the test set with prediction accuracy over 80%, sensitivity over 76%, and specificity over 82%. In addition, extended connectivity fingerprints (ECFPs) and the Toxtree software were used to analyze the functional groups and substructures linked to carcinogenicity. It was found that the results of both methods are in good agreement.

01 Apr 2013·Histology and histopathologyQ4 · BIOLOGY

Immunohistochemical evidence for an impairment of autophagy in tumorigenesis of gastric carcinoids and adenocarcinomas in rodent models and patients.

Q4 · BIOLOGY

Article

Author: Modlin, Irvin M ; Kidd, Mark ; Kodama, Yosuke ; Wang, Timothy C ; Zhao, Chun-Mei ; Fossmark, Reidar ; Viset, Trond ; Chen, Duan ; Waldum, Helge ; Vigen, Reidar Alexander

BACKGROUND/AIMAutophagy has dual roles in tumorigenesis: tumor-promoting or tumor-suppressing. The aim of the present study was to examine autophagy-related markers by immunohistochemistry in gastric carcinoids and adenocarcinomas in rodent models and patients.METHODSGastric carcinoids in Mastomys were induced by loxtidine treatment. Spontaneously developed gastric adenocarcinomas in Japanese cotton rats and INS-GAS transgenic mice were included. Patient tissue samples of gastric carcinoids or adenocarcinomas were collected. Immunohistochemistry was performed against autophagy-related gene protein-6 (ATG-6, also called beclin-1), ATG-5 and ATG-16.RESULTSIn tumor-free Mastomys, ATG-5, ATG-16 and beclin-1 were immunepositive in the gastric mucosa. In tumor-bearing Mastomys, ATG-5 and ATG-16 were negative in the tumors, whereas beclin-1 was positive in four of five animals. In carcinoid patients, ATG-5 was negative in six of ten, ATG-16 negative in nine of ten, and beclin-1 negative in three of ten patients. In cotton rats, ATG-5 and ATG-16 were negative in all tumors. Beclin-1 was negative in three of five rats. In INS-GAS mice, ATG-5 and beclin-1 were positive in the tumor area, but the numbers of immunopositive cells per gland were reduced by about 50% in comparison with wild-type mice. In adenocarcinoma patients, ATG-5 and ATG-16 were negative in eight of ten, and beclin-1 positive in all ten patients.CONCLUSIONSAn impaired autophagy took place at the stage of formation of ATG-5-ATG-12-ATG-16 complex in both gastric carcinoids and adenocarcinoma of both rodent models and patients. ATG-5 and ATG-16 might be better markers than beclin-1 in assessing autophagy in these lesions.

100 Deals associated with Lavoltidine

Login to view more data