Abstract:
:Protein stability of hypoxia-inducible factor (HIF)alpha subunits is regulated by the oxygen-sensing prolyl-4-hydroxylase domain (PHD) enzymes. Under oxygen-limited conditions, HIFalpha subunits are stabilized and form active HIF transcription factors that induce a large number of genes involved in adaptation to hypoxic conditions with physiological implications for erythropoiesis, angiogenesis, cardiovascular function and cellular metabolism. Oxygen-sensing is regulated by the co-substrate-dependent activity and hypoxia-inducible abundance of the PHD enzymes which trigger HIFalpha stability even under low oxygen conditions. Because HIFalpha itself is notoriously reluctant to the development of antagonists, an increase in PHD activity would offer an interesting alternative to the development of drugs that interfere specifically with the HIF signalling pathway. Interestingly, among the recently discovered PHD interacting proteins were not only novel downstream targets but also upstream regulators of PHDs. Their PHD isoform-specific interaction offers the possibility to target distinct PHD isoforms and their non-identical downstream signalling pathways. This review summarizes our current knowledge on PHD interacting proteins, including upstream regulators, chaperonins, scaffolding proteins, and novel downstream transcription factors.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Wenger RH,Camenisch G,Stiehl DP,Katschinski DMdoi
10.2174/138161209789649411subject
Has Abstractpub_date
2009-01-01 00:00:00pages
3886-94issue
33eissn
1381-6128issn
1873-4286pii
CPD-Roland H. Wenger (Kietzman)journal_volume
15pub_type
杂志文章,评审abstract::Tumor metastasis is an important prognostic factor regarding long-term survival rate of cancer patients. At present, no imaging modality or technique is ideal for diagnosis of metastases. Molecular imaging has provided a fantastic tool for tumor metastases imaging. Based on the current medical imaging tools such as ma...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151027153943
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:In the last decade, the development of anti-inflammatory strategies emerged as new trend in cardiovascular (CV) pharmacotherapy. Anti-inflammatory properties have been previously identified in different classes of drugs used in primary CV prevention. However, the extent to which the modification of inflammat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160822124546
更新日期:2016-01-01 00:00:00
abstract::Recent decades mark a great progress in the treatment of HIV infection. What was once a deadly disease is now a chronic infection. However, HIV-infected patients are prone to develop comorbidities, which severely affect their daily functions. For example, a large population of patients develop a variety of neurologica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160726113001
更新日期:2016-01-01 00:00:00
abstract::The targeting of drugs to skeletal muscle is an emerging area of research. Driven by the need for new therapies to treat a range of muscle-associated diseases, these strategies aim to provide improved drug exposure at the site of action in skeletal muscle with reduced concentration in other tissues where unwanted side...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140929095755
更新日期:2015-01-01 00:00:00
abstract::Metabolic syndrome (MetS) which is caused by poor dietary habits and sedentary behavior is a serious global health problem. MetS is a cluster of risk factors, represented by central obesity, hyperglycemia, dyslipidemia, and hypertension. In the 21st century, MetS and associated comorbidities, including obesity, diabet...
journal_title:Current pharmaceutical design
pub_type: 社论
doi:10.2174/138161282639201110165712
更新日期:2020-01-01 00:00:00
abstract::Aim of the presented study was to investigate the role of stromal derived factor 1 (SDF-1α) in mobilizing stem cells in combination with endothelial progenitor cell (EPC) transplantation in a regenerative strategy for myocardial infarction therapy in a murine ischemia/reperfusion model. Initially bone marrow was eradi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990443
更新日期:2014-01-01 00:00:00
abstract::Vasopressin (AVP) secretion and release are regulated by a number of central nervous system sites that receive peripheral signals from the osmoreceptors and baroreceptors. Aim of this paper is to review anatomical pathways and neurotransmitters involved as well as drugs affecting AVP secretion. ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802651607
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:The emerging evidence has recently shown an evident dependence between recently identified salusin peptides and atherosclerosis, and their important roles as endogenous modulators of atherogenesis. It was reported that the development of atherosclerosis could also be affected by endogenous salusin- β overproduc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666180607124531
更新日期:2018-01-01 00:00:00
abstract::Mast cells are important in the development of allergic and anaphylactic reactions, but also in acquired and innate immunity. There is also increasing evidence that mast cells participate in inflammatory diseases, where they can be activated by non-allergic triggers, such as neuropeptides and cytokines, often having s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800165997
更新日期:2012-01-01 00:00:00
abstract::Mass spectrometry information has long offered the potential of discovering biomarkers that would enable clinicians to diagnose disease, and treat it with targeted therapies. PeptideAtlas currently provides access to large-scale spectra data and identification information. This data, and the generation of targeted pep...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799277833
更新日期:2012-01-01 00:00:00
abstract::Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodil...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161210794454987
更新日期:2010-01-01 00:00:00
abstract::Cardiac arrhythmias remain a major source of morbidity and mortality in developed countries. Antiarrhythmic drug therapy was traditionally the mainstay of cardiac arrhythmia treatment; however, drug therapy of cardiac arrhythmias has been plagued by incomplete efficacy and by potentially serious adverse reactions, of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054021051
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Arterial hypertension (AH) and peripheral arterial disease (PAD) frequently coincide. While significant attention is paid to AH, PAD is often underestimated. It is known that both AH and PAD present high cardiovascular risks for ischemic events. To date, the use of the most common anti-hypertensive drugs in ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170608083605
更新日期:2017-01-01 00:00:00
abstract::The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660743
更新日期:2014-01-01 00:00:00
abstract::The receptor for urokinase plasminogen activator (uPAR) is required in hematopoietic stem/progenitor cells (HSC, HPC) mobilization in the mouse. Indeed, uPAR Ko mice are deficient both in retention and mobilization of HSC and HPC, because uPAR causes their retention in the BM through its interaction with the α4β1 inte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211796718206
更新日期:2011-01-01 00:00:00
abstract::The common mechanism of action of aspirin and the chemically unrelated non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of prostaglandin (PG) production due to interference with the enzymatic activity of cyclooxygenase (COX). These agents have long been used as effective treatments for arthritis. The r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003398753
更新日期:2000-11-01 00:00:00
abstract::Microdialysis is a technique for sampling the chemistry of the interstitial fluid of tissues and organs in animal and man. It is minimally invasive and simple to perform in a clinical setting. Although microdialysis samples essentially all small molecular substances present in the interstitial fluid the use of microdi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384105
更新日期:2004-01-01 00:00:00
abstract::Melanoma is the deadliest type of skin cancers, accounting for more than 80% of skin cancer mortality. Although melanoma was known very early in the history of medicine, treatment for this disease had remained largely the same until very recently. Previous treatment options, including removal surgery and systemic chem...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200130091318
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Nuts have been an indispensable component of the human diet for hundreds because of their unique nutrient composition and are thought to play a beneficial part in the prevention of cardiovascular diseases. OBJECTIVE:To evaluate the extent, validity and presence of evidence for studies investigating the impa...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
doi:10.2174/1381612822666161010121356
更新日期:2017-01-01 00:00:00
abstract::This review presents a comprehensive attempt to conclude and discuss various glucose biosensors based on core@shell magnetic nanomaterials. Owing to good biocompatibility and stability, the core@shell magnetic nanomaterials have found widespread applications in many fields and draw extensive attention. Most magnetic n...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150917092528
更新日期:2015-01-01 00:00:00
abstract::Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can self-renew indefinitely, while maintaining the capacity to differentiate into useful somatic cell types, including cardiomyocytes. As such, these stem cell types represent an essentially inexhaustible source of committed human cardiomyo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788923804
更新日期:2009-01-01 00:00:00
abstract::Protein kinases are potential targets of drugs to treat many human diseases. Intensive efforts have been made to develop protein kinase inhibitors, but a major challenge is achieving specificity. Exploiting regulatory elements outside the ATP binding pocket, such as the substrate binding site, may provide an alternati...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800672741
更新日期:2012-01-01 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::Severe asthma is a complex heterogeneous disease with substantial unmet clinical need. Understanding the immunopathogenesis is likely to provide insights into potential novel therapies. To date researchers have focussed primarily at a single scale for example genome, cell or whole organ physiology. In this review we s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795429028
更新日期:2011-01-01 00:00:00
abstract::Tumour resistance to anticancer agents remains a challenge in oncological practice, because it results in exposure to toxicities, unnecessary costs and, most importantly, delay of a potentially more effective treatment. Drug uptake by tumours may be impaired by several resistance pathways. Reasons for primary resistan...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786404344
更新日期:2008-01-01 00:00:00
abstract::CD1 molecules are a family of non-polymorphic, class I antigen-presenting glycoproteins, which bind and present amphiphilic lipid antigens for recognition to T cells. Two groups of CD1 molecules are involved in presentation of self and foreign lipid antigens: group 1 (CD1a, CD1b and CD1c) and group 2 (CD1d). Crystal s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789105108
更新日期:2009-01-01 00:00:00
abstract::Metal ions that leach into biotherapeutic drug product solution during manufacturing and storage, result in contamination that can cause physico-chemical degradation of the active molecule. In this review, we describe various mechanisms by which metal ion leachates can interact with therapeutic proteins and antibodies...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990063
更新日期:2014-01-01 00:00:00
abstract::The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticle...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150901104601
更新日期:2015-01-01 00:00:00
abstract::The epidermal growth factor receptor (EGFR) has been widely used as a target for novel anticancer agents, such as blocking antibodies and small molecular weight tyrosine kinase compounds. In spite of recent advances in cancer cell biology, leading to the introduction of clinically active new drugs, such as cetuximab, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207782360564
更新日期:2007-01-01 00:00:00
abstract::The increasing prevalence of persistent biofilm infections, such as wound infections, chronic lung infections or medical device- related infections, which usually tolerate conventional antibiotic treatment, calls for the development of new therapeutic strategies. To date, antimicrobial peptides (AMPs) are considered a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140905124312
更新日期:2015-01-01 00:00:00