Abstract:
:Recent advances in the biological and analytical sciences have led to unprecedented interest in the discovery and quantitation of endogenous molecules that serve as indicators of drug safety, mechanism of action, efficacy, and disease state progression. By allowing for improved decision-making, these indicators, referred to as biomarkers, can dramatically improve the efficiency of drug discovery and development. Mass spectrometry has been a key part of biomarker discovery and evaluation owing to several important attributes, which include sensitive and selective detection, multi-analyte analysis, and the ability to provide structural information. Because of these capabilities, mass spectrometry has been widely deployed in search for new markers both through the analysis of large molecules (proteomics) and small molecules (metabonomics). In addition, mass spectrometry is increasingly being used to support quantitative measurement to assist in the evaluation and validation of biomarker leads. In this review, the dual role of mass spectrometry for biomarker discovery and measurement is explored for both large and small molecules by examining the key technologies and methods used along the continuum from drug discovery through clinical development.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Ackermann BL,Hale JE,Duffin KLdoi
10.2174/138920006777697918subject
Has Abstractpub_date
2006-06-01 00:00:00pages
525-39issue
5eissn
1389-2002issn
1875-5453journal_volume
7pub_type
杂志文章,评审abstract::Etoposide (VP-16), a DNA topoisomerase II poison widely used as an antineoplastic agent is also known to cause leukemia. One of its major metabolic pathways involves O-demethylation to etoposide catechol (etoposide-OH) by cytochrome P450 3A4 (CYP3A4). The catechol metabolite can undergo sequential one- and two-electro...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920006779010638
更新日期:2006-12-01 00:00:00
abstract::Pharmacokinetic studies conducted in patients with CRF demonstrate that the nonrenal clearance of multiple drugs is reduced. Although the mechanism by which this occurs is unclear, several studies have shown that CRF affects the metabolism of drugs by inhibiting key enzymatic systems in the liver, intestine and kidney...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200033489532
更新日期:2003-04-01 00:00:00
abstract::The biochemical activities of plant flavonoids and stilbenoids point to many health-related applications, hampered however by a low bioavailability associated with rapid metabolic modification. A possible approach to overcome this obstacle is the development of prodrugs. In this review we provide some background infor...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200214666131211160005
更新日期:2014-01-01 00:00:00
abstract::Bioavailability of orally administered drugs can be influenced by a number of factors including release from the formulation, dissolution, stability in the gastrointestinal (GI) environment, permeability through the gut wall and first-pass gut wall and hepatic metabolism. Although there are various enzymes in the gut ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920010794328913
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:The management of ischemic nephropathy due to atherosclerotic renal artery stenosis has become increasingly conservative in the modern era, with current guidelines recommending optimized medical therapy as the initial step. The doubts raised by the recently published trials of revascularization strategies ha...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160219114443
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Mutation in the B RAF at V600E has been well implicated in the carcinogenesis that makes it as an attractive therapeutictarget. In the present study, we sought to identify the basis of V600E mutation at functional and structural grounds. The study also endeavors in identification of small molecule as a poten...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200218666170503114611
更新日期:2017-07-21 00:00:00
abstract::The possibility to treat central nervous system (CNS) disorders is strongly limited by the poor access of many therapeutic agent to the target tissues. This is mainly due to the presence of the blood-brain barrier (BBB), formed by a complex interplay of endothelial cells, astrocyte and pericytes, through which only se...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012798356943
更新日期:2012-01-01 00:00:00
abstract::For the pharmaceutical industry, one of the challenges in evaluating the risk of future compound attrition at the discovery stage is the successful prediction of the major routes of clearance in humans. For compounds cleared by metabolism, such information will help to avoid the development of compounds that will exhi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200033489235
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Wound healing is a composite and vital process in which devitalized tissue layers and cellular structures repair themselves. Bronchiolitis is generally prompted by respiratory syncytial virus or human metapneumovirus; this condition is an acute inflammatory injury of bronchioles. Heart problems that develop ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666151210124713
更新日期:2016-01-01 00:00:00
abstract::Currently the major research highlights of bioengineering and medical technology are directed towards development of improved diagnostic techniques to screen complex diseases. Screening requirements are to identify the cause of illnesses, monitor improvement or progression of the state of diseases such as cancer, card...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:
更新日期:2015-01-01 00:00:00
abstract::With the advances in recombinant DNA biotechnology, molecular biology and immunology, the number of biotech drugs, including peptides, proteins and monoclonal antibodies, available for clinical use has dramatically increased in recent years. Although pharmacokinetic principles are equally applicable to the large molec...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009789895499
更新日期:2009-09-01 00:00:00
abstract::Accompanying with hot discussions on developing multi-target drugs for the therapy of multi-gene diseases, herbal medicines are receiving more and more attention worldwide in both academic and industrial fields. Pharmacokinetic and metabolic research is one of the important issues for intensive understanding of therap...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012803341285
更新日期:2012-11-01 00:00:00
abstract::Graphene and its modified nano-composites have gained much attention in recent times in cancer therapy as nanotheranostics due to low production cost, ease in synthesis and physicochemical properties (ultra-large surface area with planar structure and π-π conjugation with the unsaturated and aromatic drugs/biomolecule...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200215666141125120633
更新日期:2015-01-01 00:00:00
abstract::The present review aims to give an overview of the cytochrome P450 8B (CYP8B) and cytochrome P450 4A (CYP4A) subfamilies in relation to biosynthesis of bile acids, in particular trihydroxy bile acids. Trihydroxy bile acids are basically required in most species and have an impact on cholesterol and lipid metabolism. T...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008784220574
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Acute Kidney Injury (AKI) is a sudden decrease in kidney function. In the early period, the highest percentage of AKI occurs among newborns hospitalized in the neonatal intensive care units, especially premature neonates. The prognosis of AKI depends on the type and severity of the cause of an injury, the ac...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200220666190321142417
更新日期:2019-01-01 00:00:00
abstract::Understanding the mechanism of action of organophosphates (OP)/nerve agents -- irreversible acetylcholinesterase (AChE, EC 3.1.1.7) inhibition at the cholinergic synapses followed by metabolic dysbalance of the organism -- two therapeutic principles for antidotal treatment are derived. The main drugs are anticholinerg...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920007782798144
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:Thiopurine antimetabolites are important agents for the treatment of severe diseases, such as acute lymphoblastic leukemia and inflammatory bowel disease. Their pharmacological actions depend on biotransformation into active thioguanine-nucleotides; intracellular metabolism is mediated by enzymes of the salv...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160303104153
更新日期:2016-01-01 00:00:00
abstract::The in vivo hepatic clearance of tanshinone IIA in the rat was predicted using microsome, cytosol and S9 fractions combined with two different cofactor systems, NADPH-regenerating and UDPGA system. Two different models, the well stirred model and the parallel-tube model, were used in predicting the in vivo clearance i...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920008783331103
更新日期:2008-01-01 00:00:00
abstract::The M2 proton channel is translated by the M gene segment of influenza viruses, and has been adopted as an attractive target for influenza A viruses, on which a series of adamantane-based drugs act. However, recently epidemic influenza viruses have had strong resistant effects against the adamantane-based drugs. In th...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200215666140605130406
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Increasing incidences of type 2 diabetes make it necessary to have a better understanding of the risk factors for its prediction. Taking a note of resilience in risk factors, dynamics of the emerging factors other than traditional ones are showing a great interest in recent years which imprints a significant...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180628170431
更新日期:2018-01-01 00:00:00
abstract::In vitro models of the liver using isolated primary hepatocytes have been used as screens for measuring the metabolism, toxicity and efficacy of xenobiotics, for studying hepatocyte proliferation, and as bioartificial liver support systems. Yet, primary isolated hepatocytes rapidly lose liver specific functions when m...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920005774832632
更新日期:2005-12-01 00:00:00
abstract::Advances in high-throughput technologies to measure genome-scale changes of genes, proteins, and other biomolecular components ('omics') in complex biological systems have dramatically revolutionized biomedical research. However, the benefits of utilizing omics information in drug development have not yet been fully r...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008786927802
更新日期:2008-12-01 00:00:00
abstract:: ...
journal_title:Current drug metabolism
pub_type: 社论
doi:10.2174/138920021914181211113837
更新日期:2018-01-01 00:00:00
abstract::This review focuses primarily on the mammalian medium and long-chain fatty acid coenzyme A ligases that have been implicated in the metabolism of xenobiotic carboxylic acids such as pesticides, arylpropionate non steroidal anti-inflammatory drugs and the hypolipidaemic clofibrate and its congeners. Evidence of multipl...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200003339261
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile. OBJECTIVE:This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites. METHOD:An exhaustive litera...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160125113806
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:ET-26 hydrochloride is a novel intravenous anesthetic, approved for clinical trials, that produces a desirable sedative-hypnotic effect with stable myocardial performance and mild adrenocortical suppression in rats and beagle dogs. The objective of this study was to assess the absorption, distribution, metab...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666191223105504
更新日期:2019-01-01 00:00:00
abstract::Transporters for organic anions and organic cations in kidney, liver, intestine, brain, and placenta play essential roles in drug disposition. The cloning and characterization of these transporters have significantly advanced our understanding of the molecular and cellular mechanisms of the drug disposition process. T...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200043489207
更新日期:2004-02-01 00:00:00
abstract::It has long been suggested that some of the neuropharmacological, neurochemical and behavioural effects of ethanol are mediated by its first metabolite, acetaldehyde. In spite of the well documented psychoactivity of acetaldehyde, the precise role of this compound in alcohol abuse remains a matter of intense debate am...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920007782109797
更新日期:2007-10-01 00:00:00
abstract:BACKGROUND:Malignant tumors are the leading cause of death in humans. Due to the tedious efforts and investigations made in the field of marine drug discovery, there is now a scientific bridge between marine and pharmaceutical sciences. However, currently only few marine drugs have been lined towards anticancer directi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170221105402
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:In recent times, herbals or phytomedicines have become very popular due to their global acceptance as a complementary and alternative remedy. While modern drugs are commercially available only after laboratory validations, clinical trials, as well as approval from drug regulatory authorities, majority of the...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200220666190325141422
更新日期:2019-01-01 00:00:00