Abstract:
:Over the past decade, Lymphocyte Function-Associated Antigen-1 (LFA-1, alphaLbeta2, CD11a/CD18) has emerged as an attractive therapeutic target for the treatment of multiple inflammatory diseases. Its established role in the trafficking and activation of leukocytes coupled with the recent elucidation of the global conformational changes that govern its function continue to drive pharmaceutical interest in this target. This sustained interest has led to the implementation of numerous drug discovery strategies leading to the development of antibodies, peptidomimetics, and small molecules that block LFA-1 function. The most successful demonstration of clinical efficacy to date has been with Raptiva, a humanized anti-LFA-1 antibody. In clinical trials of patients with moderate to severe psoriasis, improvements in several disease specific parameters including the Psoriasis Area and Severity Index (PASI) were observed. This review article will provide an overview of LFA-1 biology and structural regulation, as well as strategies that have been adopted in pursuit of effective therapies. Recent findings with different classes of small molecule antagonists will be highlighted with an emphasis on how their different mechanisms of action on the inserted domain (I domain) of CD11a have impacted our understanding of LFA-1 function and illuminated other potential avenues for therapeutic intervention.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Giblin PA,Lemieux RMdoi
10.2174/138161206777947731subject
Has Abstractpub_date
2006-01-01 00:00:00pages
2771-95issue
22eissn
1381-6128issn
1873-4286journal_volume
12pub_type
杂志文章,评审abstract::Regulation of cellular redox balances is important for the homeostasis of human health. Thus, many important human diseases, such as inflammation, diabetes, glaucoma, cancers, ischemia and neurodegenerative diseases, have been investigated in the field of reactive oxygen species (ROS) and oxidative stress. To overcome...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797052600
更新日期:2011-01-01 00:00:00
abstract::Severe sepsis leading to shock is the principal cause of death in intensive care units. It is a systemic inflammatory response caused by excessive secretion of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFalpha) and reactive oxygen species (ROS), mainly induced by endotoxin (a major component of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054864894
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Ximelagatran has been approved in Europe for VTE prophylaxis in orthopedic surgery at fixed doses and without laboratory monitoring. Aim of the study was to evaluate safety and efficacy of ximelagatran in a meta-analysis of prophylaxis and/or treatment randomized controlled trials. METHODS:Absolute risk of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析
doi:10.2174/138161205774580534
更新日期:2005-01-01 00:00:00
abstract::Drug discovery is generally considered as a costly affair and it takes approximately 15 years to reach a new chemical entity into the market. Among the recent potent drug molecules with most effective pharmacological properties, very few reached for Phase I clinical trial in humans. Unfortunately, the historical avera...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190618121553
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Tissue engineering (TE) is a promising solution for orthopaedic diseases such as bone or cartilage defects and bone metastasis. Cell culture in vitro and scaffold fabrication are two main parts of TE, but these two methods both have their own limitations. The static cell culture medium is unable to achieve m...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190301142833
更新日期:2018-01-01 00:00:00
abstract::The metabolic syndrome (MetS) represents a cluster of medical disorders, such as hyperglycemia, dyslipidemia, hypertension, and abdominal obesity that, when occurring together, increase the risk of developing cardiovascular disease. The role of food and nutrients in the aetiology of chronic diseases has become clearer...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612819666131206112144
更新日期:2014-01-01 00:00:00
abstract::Despite the significant progresses made in antiretroviral therapy, current drugs still cannot cure or prevent HIV infection. And all drugs continue to select for drug-resistant HIV strains. Consequently, new antiretroviral drugs are constantly being developed. To ensure safety, these drugs are usually designed to inhi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043382422
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Intracerebral hemorrhage is one of the most common injuries in vehicle accidents. The aim of this paper is to survey the injury mechanism of intracerebral hemorrhage in vehicle accidents, including contusion, subarachnoid hemorrhage (SAH), subdural hematoma (SDH) and diffuse axonal injury (DAI). METHODS:A c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666161118144829
更新日期:2017-01-01 00:00:00
abstract::Carboxylic acids are an important natural component as a final product or intermediates for syntheses. They are produced in plants, animals and also as products from biotechnological processes. This review presents the use of single hydroxide particles and layered double hydroxides as alternative adsorbents to remove ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666191226103623
更新日期:2020-01-01 00:00:00
abstract:AIMS:To compare the efficacy of pemafibrate (PF) and fenofibrate (FF) in treating dyslipidemia. METHODS:A comprehensive search was performed on the public database to identify relevant randomized controlled trials (RCTs), which compared the effects of PF and FF treatment in lipid parameters among patients with dyslipi...
journal_title:Current pharmaceutical design
pub_type: meta分析
doi:10.2174/1381612825666191126102943
更新日期:2019-01-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel member of the secretin/glucagon/vasoactive intestinal peptide (VIP) superfamily. In vertebrates, including avians, it occurs in two forms: PACAP(38) and PACAP(27). PACAP structure is well conserved during evolution, being identical in mammals, and s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033391586
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Approximately 10-15% of patients on DOACs have to interrupt their anticoagulant before an invasive procedure every year. The perioperative management and monitoring of DOACs have proved to be challenging, as differences in patients' status and in the invasiveness of each procedure develop different situation...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181226154746
更新日期:2018-01-01 00:00:00
abstract::Since ancient times the operation of the brain has elicited more than usual interest. Data mining of the human genome is revealing that many CNS abnormalities have a genetic component. As yet this information can not be used directly to cure or ameliorate specific CNS disorders although this is regarded as having grea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023394250
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Inhibition of hepatic fibrosis is an attainable objective in managing the chronic liver disease. The present study aimed to investigate possible defensive effects of metformin on the activities of antioxidant enzymes, hydroxyproline content, and biochemical factors in bile duct ligation (BDL)-induced cholest...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666181003114108
更新日期:2018-01-01 00:00:00
abstract::Pro-rich antimicrobial peptides are a group of linear peptides of innate immunity isolated from mammals and invertebrates, and characterised by a high content of proline residues (up to 50%). Members of this group are predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023395394
更新日期:2002-01-01 00:00:00
abstract::Hyperuricemia, has been traditionally related to nephrolithiasis and gout. However, it has also been associated with the development of type 2 diabetes mellitus (T2DM) and cardiometabolic and cardiovascular diseases. Pathophysiologically, elevated serum uric acid (SUA) levels may be associated with abnormal lipid and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612827666210104124320
更新日期:2021-01-04 00:00:00
abstract:BACKGROUND:The integrin family receptors stimulate the cellular proliferation and migration through the focal adhesion pathway by the activation of PTK2, VASP and TSP1 proteins. The purpose of this study was to investigate the integrin-ligated motifs through the activation of focal adhesion pathway. METHODS:A chimeric...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200311125325
更新日期:2020-01-01 00:00:00
abstract::Biodegradable particles have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. And recently, particle systems have also showed to be powerful for vaccine delivery (adjuvant) in order to solve the difficulties when conventional Alum adjuvant was used. However, in above applications, the pr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612821666150416100031
更新日期:2015-01-01 00:00:00
abstract::Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393233
更新日期:2002-01-01 00:00:00
abstract:BACKGROUNDS:Targeted therapy is the foundation of personalized medicine in cancer, which is often understood as the right patient using the right drug. Thinking from the viewpoint of determinants during personalized drug treatment, the genetics, epigenetics and metagenomics would provide individual-specific biological ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181106102111
更新日期:2018-01-01 00:00:00
abstract::Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of foodstuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human di...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990407
更新日期:2013-01-01 00:00:00
abstract::The formation of liposomes, nanoparticle micelles, and related systems by mixtures of drugs and/or surfactants is of major relevance for the design of drug delivery systems. We can design new systems using different compounds. Traditionally these systems are created by trial and error using experimental data. However,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160513150054
更新日期:2016-01-01 00:00:00
abstract::Commonly, the angiogenic growth factors signify healing. However, gastrointestinal ulceration is still poorly understood particularly with respect to a general pharmacological/pathophysiological role of various angiogenic growth factors implemented in growth factors wound healing concept. Thereby, we focused on the st...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180712110447
更新日期:2018-01-01 00:00:00
abstract::Quinone based bioreductive drugs have, potentially, a very versatile use in cancer chemotherapy. They can be activated by DT-diaphorase and hence can be used to target tumour types rich in this (O2)-independent reductase enzyme. Small molecular modifications can substantially reduce specificity for DT-diaphorase and u...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023394548
更新日期:2002-01-01 00:00:00
abstract::Growth differentiation factor 5 (GDF5) is a member of the bone morphogenic protein (BMP) family and plays critical roles in organ development processes including bone, cartilage, ligament, and joint formation. GDF5 is expressed in the cartilage primordium in the early limb development, and in the interzone of joint fo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319190003
更新日期:2013-01-01 00:00:00
abstract::HIV infection remains incurable although several anti-HIV drugs have been identified and developed. Among these the nucleoside analogues were and remain in the forefront of anti-HIV chemotherapeutic regimens. Most of these nucleoside analogues are modified mainly in the sugar moiety. In general, they lack a free hydro...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612024607171
更新日期:2002-01-01 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::Obesity was first described as a low-grade inflammatory condition more than a decade ago. However, it is only relatively recently that obese individuals have been described with increased macrophage infiltration of adipose tissue, as well as an increase in the number of "M1" or "classically activated" macrophages. Fur...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784246153
更新日期:2008-01-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are a group of aquired hematopoietic disorders characterized by ineffective hematopoiesis, and increased risk of progression of acute myeloid leukemia. For a long period of time, the standard therapy for MDS was hematopoietic stem cell transplantation, however DNA methyltransferase inhi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811209023204
更新日期:2012-01-01 00:00:00
abstract::Vascular disorders, resulting from endothelial cell dysfunction, may be caused by various stimuli, including infectious pathogens, cytotoxic reagents, and pathophysiological mechanisms mediated by immune responses. Endothelial cell dysfunction characterized by apoptosis and abnormal immune activation is, at least in p...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043453469
更新日期:2004-01-01 00:00:00