Abstract:
:The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated Cl- channel whose major function is to facilitate epithelial fluid secretion. Loss-of-function mutations in CFTR cause the genetic disease cystic fibrosis. CFTR is required for transepithelial fluid transport in certain secretory diarrheas, such as cholera, and for cyst expansion in autosomal dominant polycystic kidney disease. High-throughput screening has yielded CFTR inhibitors of the thiazolidinone, glycine hydrazide and quinoxalinedione chemical classes. The glycine hydrazides target the extracellular CFTR pore, whereas the thiazolidinones and quinoxalinediones act at the cytoplasmic surface. These inhibitors have been widely used in cystic fibrosis research to study CFTR function at the cell and organ levels. The most potent CFTR inhibitor has IC50 of approximately 4 nM. Studies in animal models support the development of CFTR inhibitors for antisecretory therapy of enterotoxin-mediated diarrheas and polycystic kidney disease.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Verkman AS,Synder D,Tradtrantip L,Thiagarajah JR,Anderson MOdoi
10.2174/13816128113199990321subject
Has Abstractpub_date
2013-01-01 00:00:00pages
3529-41issue
19eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20130117-5journal_volume
19pub_type
杂志文章,评审abstract::G protein receptor kinase 2 (GRK2) has been for years mainly considered the negative regulator of the cardiac β adrenergic signaling. However GRK2 is a ubiquitous molecule and its kinase activity and scaffold properties brought to several investigations which have evidenced its involvement in pathophysiology of extra-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799040493
更新日期:2012-01-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease worldwide. This is primarily driven by the global epidemic of obesity and diabetes as well as the aging of the general population. Most of the epidemiology data of NAFLD for North America are published from stud...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200303114934
更新日期:2020-01-01 00:00:00
abstract::Donkey's milk is the best substitute of human milk for its content in lactose, proteins, minerals, and omega-3 fatty acids. Here, we have evaluated the effects of colostrum and milk from donkeys (Martina Franca breed) on the function of human peripheral blood mononuclear cells (PBMCs) at different intervals from lacta...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161207783018590
更新日期:2007-01-01 00:00:00
abstract::Treatment of chronic lymphocytic leukemia (CLL) has recently undergone revolutionary changes. Two large randomized trials demonstrated superiority of chemoimmunotherapy combining fludarabine and cyclophosphamide with monoclonal anti-CD20 antibody rituximab (FCR) over fludarabine and cyclophosphamide (FC) alone in firs...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212801227096
更新日期:2012-01-01 00:00:00
abstract::Pancreatic cancer is one of the most fatal human malignancies. Though a relatively rare malignancy, it remains one of the deadliest tumors, with an extremely high mortality rate. The prognosis of patients with pancreatic cancer remains poor; only patients with small tumors and complete resection have a chance of a com...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128112092395
更新日期:2012-01-01 00:00:00
abstract::Neurodegenerative disorders are one of the most critical public health concerns of our times. Regrettably, therapeutic interventions currently available have shown only partial benefits to patients affected by one of these disorders. Although the important advances made during the last decades, several questions regar...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151223103038
更新日期:2016-01-01 00:00:00
abstract::The review examines the multifaceted interactions between cholinergic transmission and beta-amyloid suggesting a continuum in the action of the peptide that at low concentrations (picomolar-low nanomolar) may directly stimulate nicotinic cholinergic receptor while desensitizing them at increasing concentrations (high ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990503
更新日期:2014-01-01 00:00:00
abstract::Toll-like receptors (TLRs) have emerged as critical players in immunity. They are capable of sensing organisms ranging from protozoa to bacteria, fungi or viruses upon detection of the pathogen as well as recognizing endogenous ligands, and triggering transduction pathways. Following activation of the innate immune sy...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778743493
更新日期:2006-01-01 00:00:00
abstract::ATP-binding cassette (ABC) transporters are a huge family of ATP-dependent transmembrane proteins whose main function is exporting or importing substances or molecules through the cell membranes, plasma cell membrane, or inner membranes in organelles. They fulfill these functions by maintaining cell integrity, metabol...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160810120359
更新日期:2016-01-01 00:00:00
abstract::Severe acute respiratory syndrome-coronavirus (SARS-CoV-2, or COVID-19 virus) is a worldwide pandemic pathogen infecting 210 territories. It belongs to the family coronaviriadae and the order Nidovirales. The SARS-CoV-2 virus is a positive-sense single-stranded RNA enveloped virus that includes spike proteins projecti...
journal_title:Current pharmaceutical design
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doi:10.2174/1381612826666201222162509
更新日期:2020-12-22 00:00:00
abstract::Neuromuscular blocking agents are the leading drugs responsible for immediate hypersensitivity reactions during anaesthesia. Most hypersensitivity reactions represent IgE-mediated allergic reactions. Their incidence is estimated to be between 1 in 3,000 to 1 in 110,000 general anaesthetics. However striking variations...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786369704
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Vaginal infections caused by non-albicans species have become common in women of all age groups. The resistance of species such as Candida parapsilosis to the various antifungal agents is a risk factor attributed to these types of infections, which instigates the search for new sources of active compounds in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200317131041
更新日期:2020-01-01 00:00:00
abstract::Reverse transcriptase (RT) is one of the most important targets for HIV drug discovery. However, the emergence of resistant mutants has become one of the biggest challenges in HIV-1 RT drug discovery/development and attracted great research interests worldwide. It is particularly important to develop novel anti-HIV-1 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282005140214163439
更新日期:2014-01-01 00:00:00
abstract::In the last two decades quantitative electroencephalogram (EEG) analysis has been widely used to investigate the neurophysiological characteristics of insomnia. These studies provided evidence in support of the hypothesis that primary insomnia is associated with hyperarousal of central nervous system and altered sleep...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786549326
更新日期:2008-01-01 00:00:00
abstract::Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR signal from a biologica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140417113720
更新日期:2014-01-01 00:00:00
abstract::New biopharmaceutical molecules, potentially able to provide more personalized and effective treatments, are being identified through the advent of advanced synthetic biology strategies, sophisticated chemical synthesis approaches, and new analytical methods to assess biological potency. However, translation of many o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151216151420
更新日期:2016-01-01 00:00:00
abstract::Prevention, improved screening, and better treatment regimens have improved cancer incidence and mortality in the last decade. Chemoradiation continues to cause high morbidity in patients undergoing treatment. DNA therapeutics have the potential to modify the genes that cause tumor progression in order to produce a re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054546752
更新日期:2005-01-01 00:00:00
abstract::Withdrawn by the publisher. ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:
更新日期:2018-11-13 00:00:00
abstract::"Molecular recognition" is one of the most important molecular processes for living systems in order to maintain their life, since most of the biological functions are initiated with the process. Understanding of the process is also important for designing a new drug. Firstly, it is important to find a target of a dru...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796355100
更新日期:2011-01-01 00:00:00
abstract::siRNA-induced RNA Interference (RNAi) responses have great potential to treat human disease; however, siRNAs are highly charged macromolecules with no ability to enter cells and require a delivery agent. Peptide Transduction Domains (PTDs), also called Cell Penetrating Peptides (CPPs), are delivery peptides with the p...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319160008
更新日期:2013-01-01 00:00:00
abstract::The integrin family of cell surface receptors were principally thought to be involved in cell adhesion. Intense study has shown that these glycoproteins also regulate a diverse range of physiological processes. Inappropriate activation of integrins has been implicated in many pathological processes. Recent studies hav...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208783413284
更新日期:2008-01-01 00:00:00
abstract::There is growing evidence for the involvement of glutamatergic abnormalities in schizophrenia. Uncompetitive NMDA receptor (NMDAR) antagonists induce effects closely resembling both the positive and negative symptoms of schizophrenia; candidate risk genes for schizophrenia converge on the NMDAR expressing synapse; and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788957438
更新日期:2009-01-01 00:00:00
abstract::The development of targeted therapy drugs acting on tumor growth and progression is greatly expanding these last years. Among them kinase inhibitors have a prominent position and have demonstrated efficacy and clinical benefits in solid and hematologic malignancies. Compared to conventional systemic cytotoxic chemothe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160226132630
更新日期:2016-01-01 00:00:00
abstract::Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including cognition resulting i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803582522
更新日期:2012-01-01 00:00:00
abstract::The skin remains an attractive area for drug delivery. The skin, however, often limits the ingress of drugs, because of its very low permeability. Much research, focusing on employing a variety of physical and chemical methods, aimed at reversibly altering skin permeability in favour of compounds, has been reported. O...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150428125812
更新日期:2015-01-01 00:00:00
abstract::Parkinson's disease (PD) is one of common neurodegenerative diseases, which shows motor symptoms including tremor, bradykinesia, rigidity and postural instability. It also involves non-motor symptoms such as cognitive impairment, mental manifestation, autonomic disorder and sensory disturbance. Although treatments to ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170710163731
更新日期:2017-01-01 00:00:00
abstract::The role of polyphenols in the cardiovascular diseases prevention is still a matter of scientific discussion. However, recent clinical studies indicate that intake of anthocyanins and in a lesser extent procyanidins can participate in prevention of hypertension and type 2 diabetes. Fruits of Aronia melanocarpa (chokeb...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151112152143
更新日期:2016-01-01 00:00:00
abstract::Since the discovery of human immunodeficiency virus (HIV) as a causative agent of acquired immune deficiency syndrome (AIDS) various strategies were employed to counter its devastating actions. One such concept relies on the prevention of HIV entry into host's "competent" cells by means of compounds known as entry inh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319100003
更新日期:2013-01-01 00:00:00
abstract::Human heart has endogenous regenerative capability; however, the intrinsic repair mechanism is not sufficient to overcome the impact placed by adverse pathological conditions, such as myocardial infarction (MI). In such circumstances, the damaged tissue initiates a series of remodeling process which results in the det...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150302153138
更新日期:2015-01-01 00:00:00
abstract::Preterm birth is the leading cause of perinatal morbidity and mortality. Pathological processes that have been linked with preterm birth infection and / or intrauterine inflammation are most frequently found associated with their induction. Studies in animal models and human research showed prior infections to the ind...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2014-01-01 00:00:00