scholarly journals Hunting for cures: Genomics and new diseasecontrol strategies

2003 ◽  
Vol 25 (6) ◽  
pp. 19-21
Author(s):  
Michael Ginger
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
New Drugs ◽  
Potential Drug ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Genomic Technologies ◽  
Potential Drug Targets

New drugs are needed urgently to win the war against parasites that cause many serious diseases that are endemic or resurgent in some of the World's poorest countries. Post-genomic technologies provide a powerful resource that can be exploited during the drug-discovery process. With genome sequencers able to uncover secrets from even the most experimentally intractable of pathogens, the complete and annotated genomes from a number of the most medically important parasites are now, or will soon be, published. Already, the information that has been released from these projects has been put to good use in identifying new potential drug targets.

Marine Genetic Resources. A Source of New Drugs The Experience of the Biotechnology Sector

2009 ◽  
Vol 24 (2) ◽  
pp. 209-220 ◽  
Author(s):  
Fernando de la Calle
Keyword(s):  
Drug Discovery ◽  
Genetic Resources ◽  
Dna Analysis ◽  
Marine Organisms ◽  
New Drugs ◽  
Bioactive Molecules ◽  
Scale Production ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
The Status

AbstractThis article provides an overview of the conversion of marine genetic resources into new drugs. Three marine organisms suitable for application in human health and steps in the drug discovery process are described. Specific supply problems resulting from the minute concentration of required compounds for medicine in the natural marine source are examined. Three case studies illustrate different strategies enabling an industrial-scale production: chemical synthesis, biotechnology and fermentation. Future concepts for marine scientific research which could lead to new medical applications are considered. Besides research in unexplored deep sea areas, the “metagenomic approach” particularly might lead to significant new achievements. This DNA analysis of marine organisms facilitates the drug discovery process because it requires significantly less marine material than current approaches. Because this process, starting with the search for bioactive molecules and continuing with the production of drug-like molecules before finally reaching the status of medicine, can take up to 20 years, the development of medicine is a very long and risky venture.

scholarly journals Evaluating potential drug targets through human loss-of-function genetic variation

2019 ◽  
Author(s):  
Eric Vallabh Minikel ◽  
Konrad J Karczewski ◽  
Hilary C Martin ◽  
Beryl B Cummings ◽  
Nicola Whiffin ◽  
...  
Keyword(s):  
Drug Targets ◽  
Large Scale ◽  
Human Genetics ◽  
Positional Distribution ◽  
Model Organism ◽  
New Drugs ◽  
Potential Drug ◽  
Loss Of Function ◽  
Potential Drug Targets

AbstractHuman genetics has informed the clinical development of new drugs, and is beginning to influence the selection of new drug targets. Large-scale DNA sequencing studies have created a catalogue of naturally occurring genetic variants predicted to cause loss of function in human genes, which in principle should provide powerfulin vivomodels of human genetic “knockouts” to complement model organism knockout studies and inform drug development. Here, we consider the use of predicted loss-of-function (pLoF) variation catalogued in the Genome Aggregation Database (gnomAD) for the evaluation of genes as potential drug targets. Many drug targets, including the targets of highly successful inhibitors such as aspirin and statins, are under natural selection at least as extreme as known haploinsufficient genes, with pLoF variants almost completely depleted from the population. Thus, metrics of gene essentiality should not be used to eliminate genes from consideration as potential targets. The identification of individual humans harboring “knockouts” (biallelic gene inactivation), followed by individual recall and deep phenotyping, is highly valuable to study gene function. In most genes, pLoF alleles are sufficiently rare that ascertainment will be largely limited to heterozygous individuals in outbred populations. Sampling of diverse bottlenecked populations and consanguineous individuals will aid in identification of total “knockouts”. Careful filtering and curation of pLoF variants in a gene of interest is necessary in order to identify true LoF individuals for follow-up, and the positional distribution or frequency of true LoF variants may reveal important disease biology. Our analysis suggests that the value of pLoF variant data for drug discovery lies in deep curation informed by the nature of the drug and its indication, as well as the biology of the gene, followed by recall-by-genotype studies in targeted populations.

scholarly journals New directions for drug discovery in psychiatric disease

2002 ◽  
Vol 4 (4) ◽  
pp. 336-341
Keyword(s):  
Animal Model ◽  
Drug Discovery ◽  
Animal Models ◽  
Drug Targets ◽  
Disease Process ◽  
Psychiatric Disease ◽  
Potential Drug ◽  
New Directions ◽  
Potential Drug Targets

Although many new potential drug targets have been discovered subsequent to the cloning of the human genome and the discovery of most of the relevant receptors, the role of these receptors in psychiatric disease is still not clear. We argue that research into the disease process leading to new animal models that can be transposed to man is critical to drug discovery, and present an example of an animal model for schizophrenia using electroencephalography.

scholarly journals A Perspective on Extreme Open Science: Companies Sharing Compounds without Restriction

2019 ◽  
Vol 24 (5) ◽  
pp. 505-514 ◽  
Author(s):  
David H. Drewry ◽  
Carrow I. Wells ◽  
William J. Zuercher ◽  
Timothy M. Willson
Keyword(s):  
Dark Matter ◽  
Drug Discovery ◽  
Small Molecules ◽  
Drug Targets ◽  
Scientific Community ◽  
Kinase Inhibitors ◽  
Open Science ◽  
Potential Drug ◽  
Potential Drug Targets ◽  
Shed Light

Although the human genome provides the blueprint for life, most of the proteins it encodes remain poorly studied. This perspective describes how one group of scientists, in seeking new targets for drug discovery, used open science through unrestricted sharing of small molecules to shed light on dark matter of the genome. Starting initially with a single pharmaceutical company before expanding to multiple companies, a precedent was established for sharing published kinase inhibitors as chemical tools. The integration of open science and kinase chemogenomics has supported the study of many new potential drug targets by the scientific community.

scholarly journals In Silico Identification and Characterization of Potential Drug Targets in Bovine Herpes Virus 4, Causing Bovine Mastitis

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Mahantesh M. Kurjogi ◽  
Basappa B. Kaliwal
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
Drug Targets ◽  
Herpes Virus ◽  
Bovine Mastitis ◽  
Potential Drug ◽  
Herpès Virus ◽  
Potential Drug Targets ◽  
Identification And Characterization

The purpose of this study is to deal with aetiology causing bovine mastitis; bovine herpes virus is also responsible for causing bovine mastitis but studies on viruses have been neglected as historical mastitis research has concentrated only on bacterial pathogens. Therefore, present study aims to make an in silico identification and characterization of potential drug targets in bovine herpes virus 4 by computational methods using various bioinformatics tools. In the current investigation 5 proteins of BoHV 4 were found to be nonhomologous to the host Bos taurus; these nonhomology proteins were believed to be inevitable proteins of BoHV 4 as they were specific to the virus; however 378 proteins were homologous to the host protein. The in silico physicochemical characterization of 5 proteins of BoHV 4 indicated that all the proteins of the virus were having more or less similar characteristics. Perhaps the knowledge of the present study may help in drug discovery which have high affinity to target site. Possible drug discovery to manage bovine mastitis with a help of bioinformatics tool is more significant and, specific and, reduces time and complications involved in clinical trials.

scholarly journals Identification of Missing Carbon Fixation Enzymes as Potential Drug Targets in Mycobacterium Tuberculosis

2018 ◽  
Vol 15 (3) ◽  
Author(s):  
Amit Katiyar ◽  
Harpreet Singh ◽  
Krishna Kant Azad
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Target ◽  
Drug Targets ◽  
Metabolic Networks ◽  
Carbon Fixation ◽  
New Drugs ◽  
Metabolic Adaptation ◽  
Potential Drug ◽  
Genes Encoding ◽  
Potential Drug Targets

Abstract Metabolic adaptation to the host environment has been recognized as an essential mechanism of pathogenicity and the growth of Mycobacterium tuberculosis (Mtb) in the lungs for decades. The Mtb uses CO2 as a source of carbon during the dormant or non-replicative state. However, there is a lack of biochemical knowledge of its metabolic networks. In this study, we investigated the CO2 fixation pathways (such as ko00710 and ko00720) most likely involved in the energy production and conversion of CO2 in Mtb. Extensive pathway evaluation of 23 completely sequenced strains of Mtb confirmed the existence of a complete list of genes encoding the relevant enzymes of the reductive tricarboxylic acid (rTCA) cycle. This provides the evidence that an rTCA cycle may function to fix CO2 in this bacterium. We also proposed that as CO2 is plentiful in the lungs, inhibition of CO2 fixation pathways (by targeting the relevant CO2 fixation enzymes) could be used in the expansion of new drugs against the dormant Mtb. In support of the suggested hypothesis, the CO2 fixation enzymes were confirmed as a potential drug target by analyzing a number of attributes necessary to be a good bacterial target.

Wide Range Logarithmic Gradient Formation for Cell Response

2011 ◽  
Author(s):  
Morgan Hamon ◽  
Kirn Cramer ◽  
Sachin Jambovane ◽  
Jing Dai ◽  
Ali Khademhosseini ◽  
...  
Keyword(s):  
Drug Targets ◽  
Combinatorial Synthesis ◽  
New Drugs ◽  
Drug Discovery Process ◽  
Drug Candidates ◽  
Genomics And Proteomics ◽  
Wide Range ◽  
Gradient Formation ◽  
Human Genome Sequencing ◽  
Potential Drug Targets

Recently, the number of potential drug targets has dramatically increased because of the recent completion of the human genome sequencing and the progress in genomics and proteomics. In parallel, the number of new drugs for those targets has also been increased due to the use of combinatorial synthesis and the increased access to natural molecules [1]. However, this has not increased consequently the number of approved new drugs delivered to patients [2]. Indeed the drug discovery process is still limited by numbers of challenges; among them the need to analyze in more rapid and accurate manner precious sample of drug candidates.

scholarly journals Diamond: shedding light on structure-based drug discovery

2015 ◽  
Vol 373 (2036) ◽  
pp. 20140468 ◽  
Author(s):  
David G. Brown ◽  
Elizabeth J. Shotton
Keyword(s):  
Drug Discovery ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Potential Drug ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Drug Molecule ◽  
Structure Based Drug Design ◽  
Novel Drugs ◽  
New Interactions

Structure-based drug design has become a key tool for the development of novel drugs. The process involves elucidating the three-dimensional structure of the potential drug molecule bound to the target protein that has been identified as playing a key role in the disease state. Using this three-dimensional information facilitates the process of making improvements to the potential drug molecule by highlighting existing and possible new interactions within the binding site. This knowledge is used to inform increases in potency and selectivity of the molecules as well as to help improve other drug-like properties. The speed and numbers of samples that can be studied, combined with the improved resolution of the structures that can be obtained using synchrotron radiation, have had a significant impact on the utilization of crystallography in the drug discovery process.

scholarly journals Potential Drug Targets in the Pentose Phosphate Pathway of Trypanosomatids

2019 ◽  
Vol 25 (39) ◽  
pp. 5239-5265 ◽  
Author(s):  
Inês Loureiro ◽  
Joana Faria ◽  
Nuno Santarem ◽  
Terry K. Smith ◽  
Joana Tavares ◽  
...  
Keyword(s):  
Pentose Phosphate Pathway ◽  
Drug Targets ◽  
Redox Homeostasis ◽  
Aromatic Amino Acids ◽  
Pentose Phosphate ◽  
New Drugs ◽  
Potential Drug ◽  
Leishmania Spp ◽  
Causative Agents ◽  
Potential Drug Targets

The trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp, are causative agents of important human diseases such as African sleeping sickness, Chagas’ disease and Leishmaniasis, respectively. The high impact of these diseases on human health and economy worldwide, the unsatisfactory available chemotherapeutic options and the absence of human effective vaccines, strongly justifies the search for new drugs. The pentose phosphate pathway has been proposed to be a viable strategy to defeat several infectious diseases, including those from trypanosomatids, as it includes an oxidative branch, important in the maintenance of cell redox homeostasis, and a non-oxidative branch in which ribose 5-phosphate and erythrose 4-phosphate, precursors of nucleic acids and aromatic amino acids, are produced. This review provides an overview of the available chemotherapeutic options against these diseases and discusses the potential of genetically validated enzymes from the pentose phosphate pathway of trypanosomatids to be explored as potential drug targets.

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