Metabolomics in Drug Discovery: A Review (original) (raw)
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Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases
Indian Journal of Clinical Biochemistry, 2014
To refer to metabolomics as a new field is injustice to ancient doctors who used ants to diagnose the patients of diabetes having glycosuria. Measuring the levels of molecules in biological fluids believing them to be the representatives of biochemical pathways of carbohydrates, fats, proteins, nucleic acids or xenobiotic metabolism and deciphering meaningful data from it is what can be called as metabolomics, just as high glucose in urine suggests diabetes mellitus. Genomics, epigenetics, proteomics, transcriptomics finally converge to metabolomics, which are the signatures of mechanisms of bodily processes which is why understanding this science can have many applications. Just as a heap of stones does not make a house, having data of metabolite levels does not make it a science. Analyzing this data would help us in constructing biochemical pathways and their interactions. Analyzing the changes caused by a drug in the metabolite levels would help us in deriving the mechanisms by which the drug acts. Comparing metabolite levels in diseased with non-diseased, good-responders with poor-responders to a particular drug can help in identifying new markers of a disease or response to a drug respectively. Also, metabolite levels of an endogenous substrate can tell us the status of a person's metabolizing enzymes and help in drug dose titration. Generating hypothesis by identifying the new molecular markers and testing their utility in clinics seems to be the most promising approach in future. This review narrates the modes of quantifying and identifying metabolome, its proposed applications in diagnosis, monitoring and understanding the diseases and drug responses. We also intend to identify hindrances in using metabolomics in clinical studies or experiments.
Metabolomics as a Challenging Approach for Medicinal Chemistry and Personalized Medicine
Journal of medicinal chemistry, 2016
"Omics" sciences have been developed to provide a holistic point of view of biology and to better understand the complexity of an organism as a whole. These systems biology approaches can be examined at different levels, starting from the most fundamental, i.e., the genome, and finishing with the most functional, i.e., the metabolome. Similar to how genomics is applied to the exploration of DNA, metabolomics is the qualitative and quantitative study of metabolites. This emerging field is clearly linked to genomics, transcriptomics and proteomics. In addition, metabolomics provides a unique and direct vision of the functional outcome of an organism's activities that are required for it to survive, grow and respond to internal and external stimuli or stress, e.g., pathologies and drugs. The links between metabolic changes, patient phenotype, physiological and/or pathological status and treatment are now well established and have opened a new area for the application of metabolomics in the drug discovery process and in personalized medicine.
Metabolomics and Biomarkers for Drug Discovery
Metabolites, 2018
Metabolomics and biomarkers are increasingly used in drug discovery and development, and are applied to personalized medicine. Progress in these research areas has increased our understanding of disease pathology and improved therapeutic strategies for many diseases with unmet challenges. Further advances will ultimately result in the development of better drugs and breakthrough therapies, which will benefit millions of patients suffering from chronic and life-threatening diseases worldwide.
Metabolomics: a global biochemical approach to drug response and disease
2008
Metabolomics is the study of metabolism at the global level. This rapidly developing new discipline has important potential implications for pharmacologic science. The concept that metabolic state is representative of the overall physiologic status of the organism lies at the heart of metabolomics. Metabolomic studies capture global biochemical events by assaying thousands of small molecules in cells, tissues, organs, or biological fluids-followed by the application of informatic techniques to define metabolomic signatures. Metabolomic studies can lead to enhanced understanding of disease mechanisms and to new diagnostic markers as well as enhanced understanding of mechanisms for drug or xenobiotic effect and increased ability to predict individual variation in drug response phenotypes (pharmacometabolomics). This review outlines the conceptual basis for metabolomics as well as analytical and informatic techniques used to study the metabolome and to define metabolomic signatures. It also highlights potential metabolomic applications to pharmacology and clinical pharmacology.
The emergence of metabolomics as a key discipline in the drug discovery process
Drug Discovery Today: Technologies, 2015
Metabolomics is a recent science that could be defined as the comprehensive qualitative and quantitative analysis of all small molecular weight compounds present in a cell, organ (including biofluids) or organism at a specific time point. More and more applications have been found these last years to metabolomics in the pharmaceutical field. Specifically in the drug discovery process, metabolomics open new perspectives, in new targets identification, in toxicological studies and in bioactive natural products discovery. The challenge in metabolomics is to find a technological approach allowing the reproducible identification and quantitation of as much metabolites as possible. In this context, mass spectrometry and NMR are emerging as key and complementary technologies.
Metabolomics in toxicology and preclinical research
ALTEX, 2013
Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for me...
P.Shanmugasundaramet al. / Journal of Pharmacy Research 2012,5(11),5210-5213www.jpronline.info, 2012
Cancer is the major cause of mortality due to lack of specific symptoms in early stage of the disease as well as the limited understanding of etiology and oncogenesis. In order to detect the disease in early stages ‘Metabolomics’, an emerging branch of ‘omics’ is widely used. Metabolomics have opened new avenues towards biomarker discovery, identification of signaling molecules associated with cell growth, cell death, cellular metabolism and acts as a diagnostic tool for early detection of cancer. NMR spectroscopy, LC/MS and GC/MS are the analytical techniques that are widely used in metabolomics. Till date so many biomarkers were identified. This article provides the summary of the need for the cancer diagnosis at early stages and the instrumental techniques for the potential biomarker discovery. Key words: Metabolomics, cancer, biomarkers, diagnostic tool.
The Potential of Metabolomics in Biomedical Applications
Metabolites
The metabolome offers a dynamic, comprehensive, and precise picture of the phenotype. Current high-throughput technologies have allowed the discovery of relevant metabolites that characterize a wide variety of human phenotypes with respect to health, disease, drug monitoring, and even aging. Metabolomics, parallel to genomics, has led to the discovery of biomarkers and has aided in the understanding of a diversity of molecular mechanisms, highlighting its application in precision medicine. This review focuses on the metabolomics that can be applied to improve human health, as well as its trends and impacts in metabolic and neurodegenerative diseases, cancer, longevity, the exposome, liquid biopsy development, and pharmacometabolomics. The identification of distinct metabolomic profiles will help in the discovery and improvement of clinical strategies to treat human disease. In the years to come, metabolomics will become a tool routinely applied to diagnose and monitor health and dis...
Novel strategies for clinical investigation and biomarker discovery: a guide to applied metabolomics
Hormone Molecular Biology and Clinical Investigation, 2019
Metabolomics is an emerging technology that is increasing both in basic science and in human applications, providing a physiological snapshot. It has been highlighted as one of the most wide ranging and reliable tools for the investigation of physiological status, the discovery of new biomarkers and the analysis of metabolic pathways. Metabolomics uses innovative mass spectrometry (MS) allied to chromatography or nuclear magnetic resonance (NMR). The recent advances in bioinformatics, databases and statistics, have provided a unique perception of metabolites interaction and the dynamics of metabolic pathways at a system level. In this context, several studies have applied metabolomics in physiology-and disease-related works. The application of metabolomics includes, physiological and metabolic evaluation/monitoring, individual response to different exercise, nutritional interventions, pathological processes, responses to pharmacological interventions, biomarker discovery and monitoring for distinct aspects, such as: physiological capacity, fatigue/recovery and aging among other applications. For metabolomic analyses, despite huge improvements in the field, several complex methodological steps must be taken into consideration. In this regard, the present article aims to summarize the novel aspects of metabolomics and provide a guide for metabolomics for professionals related to physiologist and medical applications.
Understanding Metabolomics in Biomedical Research
Endocrinology and metabolism (Seoul, Korea), 2015
The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological cond...