Abstract:
:The recent marketing of two selective cyclooxygenase-2 (COX-2) inhibitors, celecoxib and rofecoxib is remarkable considering that COX-2 was only discovered eight years ago as a growth factor- and cytokine-inducible gene. Concomitant with these pharmaceutical successes is the advances in our understanding of the molecular and structural basis for selective COX-2 inhibition. This review provides a perspective on the ongoing structure-activity relationship (SAR) efforts in the search of COX-2-specific inhibitors with particular reference to their structural basis for isozyme-specific inhibition. In addition to the existing inhibitor classes, this review will also highlight many novel structural classes which have recently emerged due to a better understanding of the active site differences between the two isozymes with a special emphasis on the modification of the well-established non-steroidal anti-inflammatory drug (NSAID) scaffold. In addition to its role in inflammation, recent studies suggest that COX-2-derived prostaglandins may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. In this review, we summarize the NSAID epidemiological evidence, studies demonstrating overexpression of COX-2 in multiple human tumors and pharmacological evidence in animal models, which indicate that COX-2 inhibitors could be used in the prevention or treatment of a broader range of disease.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Kalgutkar AS,Zhao Zdoi
10.2174/1389450013348830keywords:
subject
Has Abstractpub_date
2001-03-01 00:00:00pages
79-106issue
1eissn
1389-4501issn
1873-5592journal_volume
2pub_type
杂志文章,评审abstract::According to international guidelines, treatment of cervical cancer (CC) consists of surgery in early stages and of chemoradiation in locally advanced disease. Metastatic disease is usually treated with palliative chemotherapeutic regimens, but cytostatic drugs present significant side effects and show limited activit...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141010145547
更新日期:2014-01-01 00:00:00
abstract::Inflammatory bowel disease diagnostic and management algorithms continue to rapidly evolve. This is partly driven by advanced radiologic techniques that provide objective, non-invasive evaluations. The realms of information provided by radiology and endoscopy continue to be intertwined. This has led to the question of...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012802429633
更新日期:2012-09-01 00:00:00
abstract::Nowadays, natural compounds of plant origin with anticancer effects have gained more attention because of their clinical safety and broad efficacy profiles. Autophagy is a multistep lysosomal degradation pathway that may have a unique potential for clinical benefit in the setting of cancer treatment. To retrieve artic...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200504072635
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Nanotechnology deals with the manufacturing of materials at the atomic and molecular scale. According to the National Nanotechnology Initiative, nanotechnology denotes those structures which are nearly in 1-100 nm size regime in at least one dimension. OBJECTIVE:Nanotechnology in drug delivery has been evid...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666180131105822
更新日期:2018-01-01 00:00:00
abstract::Type 2 diabetes, which has dramatically increased during the last decade normally results from a combination of pancreatic beta cell dysfunction and insulin resistance. One of the most recent risk factors identified for type 2 diabetes is a sub-optimal fetal and neonatal environment. Numerous human epidemiological stu...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007781386866
更新日期:2007-08-01 00:00:00
abstract::Five programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for the treatment of locally advanced or metastatic urothelial carcinoma of the bladder and the upper urinary tract. Following the FDA and EMA restrictions of first-line treatment with Atezolizumab and Pembrolizumab in platinum...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200510015216
更新日期:2020-05-09 00:00:00
abstract::Human proteins are subjected to more than 200 known post-translational modifications (PTMs) (e.g., phosphorylation, glycosylation, ubiquitination, S-nitrosylation, methylation, Nacetylation, and citrullination) and these PTMs can alter protein structure and function with consequent effects on the multitude of pathways...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150202160954
更新日期:2015-01-01 00:00:00
abstract::Long term treatment with antiepileptic drugs (AEDs) is the standard therapeutic approach to eradicate seizures. However, a small but significant number of patients fail AED treatment. Intrinsic drug resistance may depend on two main and not necessarily mutually exclusive mechanisms: 1) Loss of pharmacological target (...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450033491109
更新日期:2003-05-01 00:00:00
abstract::The last 15 years have witnessed a resurgence of the role of surgical options for prevention of ischemic stroke. The landmark randomized trials including NASCET and ECST were published and explored the role of carotid endarterectomy in this regard. Patients with high grade stenosis of the internal carotid artery (> or...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007781077391
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Endometriosis (EMS) is a gynecological disease defined by the translocation and growth of endometrial tissue in other tissues or organs outside the uterus. Its clinical manifestations are dysmenorrhea, irregular menstruation, and even infertility. Although EMS is a benign disease, it has the characteristics ...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200228112344
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Gabapentin and pregabalin inhibit Ca(2+) currents via high-voltage-activated channels containing the alpha2delta-1 subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used also for the chronic pain treatment. A large number of cl...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009788982513
更新日期:2009-08-01 00:00:00
abstract::Antiphospholipid syndrome (APS) is characterized by a combination of clinical features consisted of thrombotic or pregnancy-related events and autoimmune antiphospholipid antibodies. In the 1998 International Consensus Preliminary Criteria, APS is defined by the concomitant presence of these clinical features and labo...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450054545999
更新日期:2005-08-01 00:00:00
abstract::Using a portable infusion pump, intravenous opioid patient-controlled analgesia (PCA) permits a patient to self-deliver a small bolus of opioid to achieve prompt relief without over sedation. Use of PCA for pain management is increasing in hospitals, largely because it can provide equivalent or better analgesia than c...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945005774574524
更新日期:2005-11-01 00:00:00
abstract::Excessive production of reactive oxygen species is an important mechanism underlying the pathogenesis of diabetes associated macrovascular and microvascular complications including diabetic nephropathy. Diabetic nephropathy is characterized by glomerular enlargement, early albuminuria and progressive glomerulosclerosi...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140321120635
更新日期:2014-05-01 00:00:00
abstract::The popular use of antioxidative vitamins illustrates the growing awareness of oxidative stress as an important hazard to our health and as an important factor in the ageing process. Superoxide radicals and superoxide-derived reactive oxygen species (ROS) are constantly formed in most cells and tissues. To ensure that...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450110607011505
更新日期:2006-11-01 00:00:00
abstract::The pivotal role of 5-HT in the control of appetite was formally proposed nearly 30 years ago. In particular endogenous hypothalamic 5-HT has been implicated in the processes of within meal satiation and the end state of post meal satiety. Of the numerous 5-HT receptor subtypes currently identified, 5-HT(1B) and 5-HT(...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450053174550
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:To investigated the use of mixed treatment comparison (MTC) meta-analysis models to summarize results from randomized clinical trials (RCTs) on approved pharmacological treatments for neovascular age-related macular degeneration (AMD). METHODS:The number of patients with visual loss or visual gain of 3 or mo...
journal_title:Current drug targets
pub_type: 杂志文章,meta分析,评审
doi:10.2174/138945011794182665
更新日期:2011-02-01 00:00:00
abstract::The emergency of responsive drug delivery systems has contributed to the reduced cytotoxicity, the improved permeability in tissues and extended circulation time of the active drug. Of particular, enzyme-responsive nanoplatforms have attracted a lot due to the specificity and efficiency of an enzyme-catalyzed reaction...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450122666210114095614
更新日期:2021-01-13 00:00:00
abstract::Crohn's disease (CD) and ulcerative colitis (UC), two chronic and relapsing inflammatory bowel diseases (IBD), are supposed to develop in genetically-predisposed individuals as a result of an excessive immune mucosal response directed against normal components of the gut microbiota. There is also evidence that defects...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990157
更新日期:2013-11-01 00:00:00
abstract::Autophagy is a process the primary role of which is to clear up damaged cellular components such as long-lived proteins and organelles, thus participating in the conservation of different cells. Osteoporosis associated with aging is characterized by consistent changes in bone metabolism with suppression of bone format...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666180626120852
更新日期:2019-01-01 00:00:00
abstract::The genus Zanthoxylum (Rutaceae) comprises about 250 species, of which many are used as food, often as condiments, substituting pepper due to the pungent taste of fruits, seeds, leaves, and bark, and therapeutic remedies especially in Eastern Asian countries and in Central America. The whole plant is also consumed as ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011798184128
更新日期:2011-12-01 00:00:00
abstract::Seventy five percent of hospitalized patients with Crohn's disease suffer from malnutrition. One third of Crohn's disease patients have a body mass index below 20. Sixty percent of Crohn's disease patients have sarcopenia. However some inflammatory bowel disease (IBD) patients are obese or suffer from sarcopenic-obesi...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450115666140930150047
更新日期:2014-01-01 00:00:00
abstract::Adipose tissue plays an active role in energy balance because it is not only a lipid storing and mobilizing tissue but consists of functionally specialized tissues able to produce heat (in brown adipose tissue) and to produce or release a vast number of so called adipokines or adipocytokines. These consist of polypept...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450043490523
更新日期:2004-04-01 00:00:00
abstract:BACKGROUND:Global death rate due to cardiovascular diseases (CVDs) is highest as compared to other ailments. Principal risk factor associated with CVDs is hypertension. Major classes of current antihypertensive (AHT) therapies include angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs)...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160711163119
更新日期:2017-01-01 00:00:00
abstract::The fibrinolytic system consists of a balance between rates of plasminogen activation and fibrin degradation, both of which are finely regulated by spatio-temporal mechanisms. Three distinct inhibitors of the fibrinolytic system that differently regulate these two steps are plasminogen activator inhibitor type-1 (PAI-...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666190715102510
更新日期:2019-01-01 00:00:00
abstract::Parkinson's disease (PD) is characterized by relatively selective degeneration of dopaminergic neurons in the substantia nigra and loss of dopamine in the striatum. More than 50 epidemiological studies confirmed the low incidence of PD in smokers. Examining the distribution of subtypes of nicotinic acetylcholine recep...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012800399026
更新日期:2012-05-01 00:00:00
abstract::Epithelia are the layers of cells that form barriers between external milieu and underlying tissues and thus, are important components of most organs of the body. Epithelial layers of organs, such as the lung, are exposed to various challenges resulting in frequent injury. Epithelial wound healing represents an import...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006776818719
更新日期:2006-05-01 00:00:00
abstract::Antimicrobial resistance of human pathogenic bacteria is an emerging problem for global public health. This resistance is often associated with the overproduction of membrane transport proteins that are capable to pump chemotherapeutics, antibiotics, detergents, dyes and organic solvents out of the cell. In Gram-negat...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008785747789
更新日期:2008-09-01 00:00:00
abstract::Dysbiosis has been repeatedly observed in inflammatory bowel disease (IBD) and is now recognized as an essential factor in the gut inflammatory process. IBD is a significant burden to health-care systems, mainly due to treatment-related costs. Available treatments have several limitations: up to 30% of patients are pr...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200602125507
更新日期:2020-01-01 00:00:00
abstract::Cancer cells produce high levels of reactive oxygen species (ROS) that lead to a state of increased basal oxidative stress. Since this state of oxidative stress makes cancer cells vulnerable to agents that further augment ROS levels, the use of pro-oxidant agents is emerging as an exciting strategy to selectively targ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012802009044
更新日期:2012-07-01 00:00:00