Abstract:
:Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. In this in-depth review we discuss the genetic polymorphisms of genes encoding for glutathione S-tranferases, xanthine oxidase, thiopurine S-methyltransferase, inosine triphosphate pyrophosphatase, hypoxanthine phosphoribosyltransferase, inosine monophosphate dehydrogenase and multidrug resistance proteins. Pharmacogenetic knowledge in this field has increased dramatically and is still rapidly increasing, but the translation into practical guidelines with tailored advices will cost much effort in the near future.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Derijks LJ,Wong DRdoi
10.2174/138161210790112773subject
Has Abstractpub_date
2010-01-01 00:00:00pages
145-54issue
2eissn
1381-6128issn
1873-4286pii
CPD-Luc J.J. Derijks (Guchelaar)journal_volume
16pub_type
杂志文章,评审abstract::These are exciting times for bioinformaticians, computational biologists and drug designers with the genome and proteome sequences and related structural databases growing at an accelerated pace. The post-genomic era has triggered high expectations for a rapid and successful treatment of diseases. However, in this bio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990379
更新日期:2013-01-01 00:00:00
abstract::This review describes gene therapy strategies that take advantage of defective signal transduction pathways to selectively kill cancer cells without adversely affecting normal cells. The distinctive features of cancer cells currently exploited by gene therapy include mitosis, cell permissiveness to infection, specific...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393927
更新日期:2002-01-01 00:00:00
abstract::ATP-sensitive K+ channels, termed K(ATP) channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolari...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054546879
更新日期:2005-01-01 00:00:00
abstract::In the mid seventies a drug design programme using the Amanita muscaria constituent muscimol (7) as a lead structure, led to the design of guvacine (23) and (R)-nipecotic acid (24) as specific GABA uptake inhibitors and the isomeric compounds isoguvacine (10) and isonipecotic acid (11) as specific GABAA receptor agoni...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399608
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:Cancer is the world's second-largest cause of death, with an estimated 9.6 million fatalities in 2018. Malignant tumour (cancer) is caused by a mixture of genetic modifications due to the environmental variables that tend to activate or inactivate different genes, ultimately resulting in neoplastic transform...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200701151403
更新日期:2020-01-01 00:00:00
abstract::Surgery for epilepsy dates back to 1886 and has undergone significant developments. Today it is considered a key treatment modality in patients who are resistant to pharmacological intervention. It improves seizure control, cognition and quality of life. New technologies, advances in surgical technique and progress in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666171031101839
更新日期:2017-01-01 00:00:00
abstract::The introduction of highly active anti-retroviral therapy (HAART) for Human Immunodeficiency Virus (HIV) infection has significantly improved the life expectancy of HIV positive patients. Hepatitis C virus (HCV) co-infection is common in HIV infected patients and is now a significant cause of morbidity and mortality. ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384286
更新日期:2004-01-01 00:00:00
abstract::Recent advances in the fabrication, characterization and application of micro- and nano-particles that possess a non-uniform internal structure are reviewed. The particle structures include core-shell particles, particles with multiple cores or a multi-layered structure, porous particles with both regular and random p...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319350007
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous prete...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190329124214
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:A wide class of human diseases and neurodegenerative disorders, such as Alzheimer's disease, is due to the failure of a specific peptide or protein to keep its native functional conformational state and to undergo a conformational change into a misfolded state, triggering the formation of fibrillar cross-β s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160518141911
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment, including intellectual disability, autism, hyperactivity, and epilepsy. METHODS:This article reviews the literature pertaining to the role of synaptic dysfunction in FXS. RESULTS:In FXS, synaptic dysfunction alte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191102165206
更新日期:2019-01-01 00:00:00
abstract::A correct representation of intermolecular interaction energies is necessary for reliable drug-receptor docking studies. While ab initio quantum chemistry with extended basis sets is the most accurate tool for that purpose, its use is precluded for very large molecular complexes. This constitutes the incentive for the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777585256
更新日期:2006-01-01 00:00:00
abstract::Superparamagnetic iron oxide nanoparticles (SPIONs) comprise a fundamental technology class within the emerging field of nanomedicine, and have been extensively researched for cancer imaging and therapy. This review article will discuss the chemistry and design considerations associated with the synthesis of SPIONs an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::The search for methods to control physiological levels of carbon monoxide (CO), a vasoactive molecule, and bilibrubin, an antioxidant, have improved our understanding of the protective role of heme oxygenase (HO) against oxidative injury. HO activity can assist other antioxidant systems in diminishing the overall prod...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033453758
更新日期:2003-01-01 00:00:00
abstract::Obesity has become a serious epidemic and one of the leading global health problems. However, much of the current debate has been fractious, and etiologies of obesity have been attributed to eating behavior (i.e. fast food consumption), personality, depression, addiction or genetics. One of the interesting new hypothe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211795656855
更新日期:2011-01-01 00:00:00
abstract::Chemotherapy is one of the most frequently employed and reliable treatment options for the management of a variety of cancers. Taxanes (paclitaxel, docetaxel and cabazitaxel) are frequently prescribed to treat breast cancer, hormone refractory prostate cancer, non-small cell lung cancer and ovarian cancer. Most of the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160524144926
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Coronavirus Disease-2019 belongs to the family of viruses which cause a serious pneumonia along with fever, breathing issues and infection of lungs for the first time in China and later spread worldwide. OBJECTIVE:Several studies and clinical trials have been conducted to identify potential drugs and vaccin...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201118103416
更新日期:2020-11-17 00:00:00
abstract:BACKGROUND:Despite the limited evidence about the effect of micronutrient supplementation on the semen quality, many micronutrient supplements have been used to improve male fertility. Approximately, 40%-50% of male infertility cases in general and up to 80% in men with idiopathic infertility cases are caused by oxidat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200415173537
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:The failing heart is characterized by a depleted metabolic energy reserve and the upregulation of several molecular mechanisms leading to cardiac hypertrophy, inflammation, fibrosis, angiogenesis, and apoptosis. Dietary or non-dietary supplementation of vitamins could potentially benefit energy balance. OBJ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170321094711
更新日期:2017-01-01 00:00:00
abstract::Polyunsaturated fatty acids (PUFA) are a family of lipids including some subgroups identified by the position of the last double bond in their structure. PUFA n-3 include alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), while PUFA n-6 include linoleic acid (LA) and arachidonic a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161209789909773
更新日期:2009-01-01 00:00:00
abstract::RNA interference (RNAi) has quickly proven to be an immensely useful tool for studying gene function and validation of potential drug targets in almost all organisms that possess the required set of proteins of the interference pathway. In protozoan parasites like Plasmodium, Toxoplasma, Entamoeba, Giardia, Trypanosom...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990027
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Oxidative stress and inflammation are key parameters in developing metabolic disorders. Hence, antioxidant intake might be an appropriate approach. Several studies have evaluated the effect of coenzyme Q10 (CoQ10) supplementation on lipid profile among patients with metabolic diseases, though f...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析
doi:10.2174/1381612824666180406104516
更新日期:2018-01-01 00:00:00
abstract::The large conduit arteries of the thorax and abdomen are elastic while those in the arms and legs are muscular. Alterations in wall properties of elastic arteries occur over time and are usually permanent in nature; acute changes can, however, occur is response to a change in transmural pressure. Chronic alterations i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787354258
更新日期:2009-01-01 00:00:00
abstract::Today, in spite of being older than a century (born in 1911), the Pictet-Spengler two component reaction (PS-2CR) is still one of the most popular reactions, not only for the synthesis of tetrahydroisoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), or more complex structures containing these two privileged moieti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151231100247
更新日期:2016-01-01 00:00:00
abstract::Many of the most debilitating symptoms for psychiatric disorders such as schizophrenia remain poorly treated. As such, the development of novel treatments is urgently needed. Unfortunately, the costs associated with high failure rates for investigational compounds as they enter clinical trials has led to pharmaceutica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160127113912
更新日期:2016-01-01 00:00:00
abstract::In association with their mechanisms of self/non-self recognition (known as mating type systems), ciliates synthesize and constitutively secrete cell type-specific proteins into their extracellular medium. These proteins, designated as pheromones, have been isolated from species of Euplotes and shown to be members of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777947452
更新日期:2006-01-01 00:00:00
abstract::DNA methylation is an important regulatory component which influences phenotypes by modulating gene expression. Changes in DNA methylation may lead to altered phenotypes and ability of an organism to respond to stress leading to subsequent manifestation of life style diseases, cancer, etc. The human X chromosome repre...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990518
更新日期:2014-01-01 00:00:00
abstract::Unlike other neuroinflammatory disorders, like Parkinson's disease, Huntington's disease and multiple sclerosis, little is still known of the role of the endocannabinoid system in Alzheimer's disease (AD). This is partly due to the poor availability of animal models that are really relevant to the human disease, and t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785740027
更新日期:2008-01-01 00:00:00
abstract::Prion diseases are fatal neurodegenerative disorders associated with conformational conversion of the cellular prion protein (PrP(C)) into an isoform designated PrP(Sc). The pathogenic mechanism that links this conformational distortion with the development of prion diseases is unknown. PrP(C) is a GPI-anchored cell s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777698873
更新日期:2006-01-01 00:00:00
abstract::The survival of patients with pulmonary arterial hypertension is closely related with right ventricular function. During the progression of right ventricular remodeling, energetic metabolism shifts from oxidative mitochondrial metabolism to glycolysis. In normal physiological conditions, cardiomyocytes use major sourc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160614082712
更新日期:2016-01-01 00:00:00