Current Topics in Medicinal Chemistry - Volume 17, Issue 24, 2017

Untargeted metabolomics is a promising approach for reducing the significant attrition rate for discovering and developing drugs in the pharmaceutical industry. This review aims to highlight the practical decision-making value of untargeted metabolomics for the advancement of drug candidates in drug discovery/development including potentially identifying and validating novel therapeutic targets, creating altern Read More

Nowadays, cancer therapy remains limited by the conventional one-size-fits-all approach. In this context, treatment decisions are based on the clinical stage of disease but fail to ascertain the individual ´s underlying biology and its role in driving malignancy. The identification of better therapies for cancer treatment is thus limited by the lack of sufficient data regarding the characterization of specific biochemical signat Read More

Chronic liver diseases are one of the major causess of mortality worldwide. It can manifest through many different forms including chronic virus infection, alcohol abuse, metabolic syndromes such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. At early stages, the liver can repair the damage produced by the insult. However, upon continuous damage, the accumulation of molecules triggers fibrosis, whic Read More

Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin- induced kidney lesions in male dogs we Read More

We have developed a workflow to extract, separate, and semi-quantify bioactive oxysterols from mouse colon tissues and fecal matters using solid- and liquid-phase extractions, enzymatic and chemical modifications, and stable-isotope dilution LC/MS/MS. The method was applied to a dextran sodium sulphate (DSS)-induced mouse colitis model, which revealed that one particular dihydroxycholesterol (diOHC), 7α,25-diOHC, was Read More

We have developed a targeted metabolomics screen which consists of using two isotopically labeled glucose compounds to conduct a dual oral glucose tolerance test in rats. This dual isotopic oral glucose tolerance test (DIS-OGTT) can be used to select drug candidates that have “on”-target or have “off”-target effects on oral glucose absorption, hepatic glucose production or glucose disposal. The DIS-OGTT assay utilized intra Read More