Abstract:
:Advances in molecular medicine have revealed a key role for altered gene expression in the aetiology of many inflammatory diseases, including asthma, rheumatoid arthritis, inflammatory bowel disease and sepsis. Until recently, however, modulation of gene transcription has not been the subject of directed pharmaceutical research efforts. Notwithstanding, it is clear that the efficacy of several well-established anti-inflammatory therapeutics is mediated through their ability to modulate gene transcription. Understanding the mechanisms of action of these therapeutics and defining new gene regulatory pathways has stimulated a new wave of anti-inflammatory drug discovery. This update aims to cover our current understanding of transcription inhibitors in inflammation, including the mechanism of action of established therapeutics and the properties of new chemical entities recently described in the literature.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Manning AM,Mercurio Fdoi
10.1517/13543784.6.5.555subject
Has Abstractpub_date
1997-05-01 00:00:00pages
555-67issue
5eissn
1354-3784issn
1744-7658journal_volume
6pub_type
杂志文章abstract:INTRODUCTION:Dysregulation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is central to the pathophysiology of myeloproliferative neoplasms (MPN). Small molecule inhibitors of JAK family members are currently under investigation for the treatment of MPN. Of these, ruxolitinib ha...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.774373
更新日期:2013-06-01 00:00:00
abstract:INTRODUCTION:Melanoma is one of the most aggressive forms of cutaneous malignancies displaying a substantial mortality rate among the various forms of skin cancers. The management of patients with advanced melanoma poses a significant challenge considering that the disease is refractory to most conventional therapies. ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.884558
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Dexamethasone cipecilate is a corticosteroid nasal spray whose local efficacy durability has been improved by introduction of a liposoluble functional group to its chemical structure. This study was conducted to evaluate the efficacy of once-daily treatment with this drug in patients with perennial allergic ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,随机对照试验
doi:10.1517/13543784.2010.531258
更新日期:2010-12-01 00:00:00
abstract::Marfan syndrome is the most common genetic disorder of the connective tissue with an estimated prevalence of 1:10,000. The disease is characterised by manifestations in the cardiovascular, skeletal and ocular systems. The most severe manifestations are those of the cardiovascular system: mitral valve prolapse and dila...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.7.983
更新日期:1999-07-01 00:00:00
abstract:INTRODUCTION:Despite recent advances, pulmonary arterial hypertension (PAH) remains a devastating disease which harbors a poor prognosis. Novel therapeutic approaches directly targeting pulmonary vascular remodeling are warranted. AREAS COVERED:This review delineates the current limitations in the management of PAH an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.632408
更新日期:2012-01-01 00:00:00
abstract::Improving the tumour selectivity of cytotoxic drugs through conjugation to tumour-reactive monoclonal antibodies may lead to novel, more potent agents for cancer therapy. The maytansinoid drugs are 100- to 1000-fold more cytotoxic in vitro than current clinical anticancer drugs. We recently demonstrated that conjugati...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.2.169
更新日期:1997-02-01 00:00:00
abstract:INTRODUCTION:Aberrant regulation of platelet-derived growth factors (PDGFs) and their receptors (PDGFR) has been shown to be involved in many solid tumors, including breast cancer. PDGFR-α and PDGFR-β expressions were documented in breast cancer and are correlated with tumor aggressiveness and metastasis. Preclinical e...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.895323
更新日期:2014-05-01 00:00:00
abstract::Therapeutic angiogenesis is a novel approach to the treatment of ischaemic or occlusive coronary and peripheral vascular disease. The therapeutic concept is based on the restoration of distal blood flow by the enlargement of existing vessels and tissue perfusion by the induction of new capillaries. Initial studies hav...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.10.1319
更新日期:2004-10-01 00:00:00
abstract::Asthma and chronic obstructive pulmonary disease (COPD) are diseases of the airways with an underlying inflammatory component. The prevalence and healthcare burden of asthma and COPD is still rising and is predicted to continue to rise in the current century. The beta-agonists and corticosteroids form the basis of the...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.1.5
更新日期:2003-01-01 00:00:00
abstract::Therapeutic angiogenesis has yielded promising results in animal models, including the demonstration of newly created blood vessels, increased perfusion and functional benefits. On the other hand, clinical studies using similar methods of angiogenesis have so far been disappointing. The possibility that endothelial dy...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.1.37
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The progression of the mammalian cell cycle is driven by the transient activation of complexes consisting of cyclins and cyclin-dependent kinases (CDKs). Loss of control over the cell cycle results in accelerated cell division and malignant transformation and can be caused by the upregulation of cyclins, t...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.628985
更新日期:2011-12-01 00:00:00
abstract:INTRODUCTION:Pro-protein [corrected] convertase subtilisin kexin (PCSK)-9 is a newly discovered protein involved in intracellular and extracellular regulation of low-density lipoprotein receptor (LDLR) expression. Autosomal dominant activating mutations in PCSK-9 cause familial hypercholesterolaemia whereas inactivatin...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.679340
更新日期:2012-05-01 00:00:00
abstract::Risperidone (Risperdal) is a benzisoxazole derivative with a high affinity for serotonin 5-HT2 and dopamine D2 receptors, and some affinity for alpha- adrenergic, histamine H1 and dopamine D1 receptors. It has no anticholinergic effects. Early studies demonstrated risperidone to be an effective medication for psychoti...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.4.443
更新日期:1999-04-01 00:00:00
abstract::Tuberculosis (TB), which kills more people than any other infectious disease, was declared a global emergency by the World Health Organization in 1993. The emergence of new Mycobacterium tuberculosis strains that are resistant to some or all current antitubercular drugs seriously hampers the control of the disease. Up...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.8.1033
更新日期:2002-08-01 00:00:00
abstract::COPD is a chronic disease of the lung that is characterised by decreased air flow and associated abnormal inflammatory responses of the lungs. A total of 80% of COPD incidences are observed in patients with history of smoking tobacco. The chronic condition of COPD is characterised by airway remodelling, which leads to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.7.1069
更新日期:2007-07-01 00:00:00
abstract::The principal components of the asthmatic response are airways hyper-responsiveness, persistent inflammation and mucus hypersecretion. Although these components are inter-related, any of these can predominate at different times and for different patients and each requires a different approach to therapy. As a result o...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.6.889
更新日期:2007-06-01 00:00:00
abstract:INTRODUCTION:Asthma is a common respiratory disease characterized by airway inflammation, bronchoconstriction and airway hyperresponsiveness and symptoms such as coughing, wheezing, shortness of breath and chest tightness. Allergic rhinitis is a common comorbidity in asthma and glucocorticoids are the key stone in the ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1192124
更新日期:2016-08-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Molecules isolated from animals, insects, plants or microorganisms can provide prototypes for design of biopharmaceutical products. Some venom toxins and their derivatives are used in medicine, while others provide templates for development of new drugs. AREAS COVERED IN THIS REVIEW:The mild to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.534457
更新日期:2010-12-01 00:00:00
abstract::Insulin glargine (HOE 901) appears to be the first clinically useful extended-acting insulin preparation for 50 years. A combination of a di-arginine addition to the C-terminal of the insulin B-chain, and a glycine substitution in the A-chain, produce an insulin which is soluble at acid pH, but precipitates in sc. tis...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.3.307
更新日期:1999-03-01 00:00:00
abstract::Toll-like receptors (TLRs) form a family of pattern recognition receptors that have emerged as key mediators of innate immunity. These receptors sense invading microbes and initiate the immune response. TLR-mediated inflammation is an important pathogenic link between innate immunity and a diverse panel of clinical di...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.8.857
更新日期:2006-08-01 00:00:00
abstract:INTRODUCTION:Fibroblast growth factor receptors (FGFR 1-4) are a highly conserved family of receptor tyrosine kinases, involved in several physiological processes. Genetic aberrations of FGFRs and their ligands, fibroblast growth factors (FGFs) are involved in several pathological processes including cancer. The FGF-FG...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1838484
更新日期:2020-12-01 00:00:00
abstract::Disruption of a vulnerable atherosclerotic plaque is well-recognised as the primary cause of stroke, non-fatal myocardial infarction and sudden cardiac death. Novel therapeutic agents are being developed to stabilise such plaques. The initial evaluation of these drugs would be facilitated by the use of non-invasive im...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.5.693
更新日期:2002-05-01 00:00:00
abstract::There are several reasons to believe that agents that augment cAMP-mediated signalling in cardiac myocytes should have beneficial effects in patients with heart failure. However, clinical trials of first-generation cyclic nucleotide phosphodiesterase (PDE3) inhibitors, which raise cAMP content by blocking its hydrolys...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.5.963
更新日期:2000-05-01 00:00:00
abstract::In the last decade, transdermal delivery of testosterone (T) has been shown to be a safe and effective means of treating male hypogonadism. Transdermal T patches can provide for physiologic androgen replacement in over 90% of men with hypogonadism. In addition, T patches have been shown to be equivalent to im. T ester...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.12.1977
更新日期:1998-12-01 00:00:00
abstract:INTRODUCTION:The introduction of therapy with tumor necrosis factor antagonists (aTNF) was a cornerstone of treatment modalities in patients with ankylosing spondylitis (AS). After > 10 years of using aTNF, the introduction of aTNF therapy was a major step forward in the medical management of patients with spondyloarth...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.899351
更新日期:2014-05-01 00:00:00
abstract::Heat shock proteins are vital to cell survival under conditions of stress. They bind client proteins to assist in protein stabilization, translocation of polypeptides across cell membranes and recovery of proteins from aggregates. Heat shock protein inhibitors are a diverse group of novel agents that have been demonst...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903158934
更新日期:2009-09-01 00:00:00
abstract::A disintegrin and metalloproteases (ADAMs) are zinc-dependent trans-membrane metalloproteases that shed the extracellular domains of membrane-bound growth factors, cytokines and receptors. Key functions of ADAMs have emerged in ErbB signalling pathways as being sheddases for multiple ErbB ligands. As the ErbB pathway ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.6.591
更新日期:2005-06-01 00:00:00
abstract::Diminished efficacy in terms of clinical relapses and lesion load on magnetic resonance images for patients developing neutralising antibodies (NAbs) to recombinant IFN-beta may be found in multiple sclerosis. NAbs become detectable over the first few years of therapy, disappearing during the treatment course in some ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.7.1153
更新日期:2003-07-01 00:00:00
abstract:INTRODUCTION:Psychostimulants are first-line treatments for attention-deficit/hyperactivity disorder (ADHD), but their tolerability profiles and individual response variability fuel a continuing search for alternative medications. The observation that nicotinic agents improve cognition has led pharmaceutical companies ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.934806
更新日期:2014-08-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The sodium/hydrogen exchanger-1 (NHE-1/SLC9A1) is a ubiquitous plasma membrane protein whose main role is maintenance of intracellular pH and volume. NHE-1 plays a role in atherogenesis; however, its clinical relevance has not yet been established. AREAS COVERED IN THIS REVIEW:We herein review ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.532123
更新日期:2010-12-01 00:00:00