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 hydrolysis, have shown that chronic administration of these drugs affect survival adversely. The problem may be the non-selective activation of a broad spectrum of cAMP-regulated cellular responses these agents elicit. More selective (or alternatively selective) cyclic nucleotide PDE inhibitors might improve results by evoking a more restricted set of cellular responses.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Movsesian MAdoi
10.1517/13543784.9.5.963subject
Has Abstractpub_date
2000-05-01 00:00:00pages
963-73issue
5eissn
1354-3784issn
1744-7658journal_volume
9pub_type
杂志文章,评审abstract:INTRODUCTION:Cardiovascular disease is the leading cause of death worldwide, accounting for 30% of all deaths, with elevated blood pressure probably the most important modifiable risk factor. Worldwide, elevated blood pressure is estimated to cause 7.5 million deaths, about 12.8% of the total of all annual deaths. New ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.797962
更新日期:2013-07-01 00:00:00
abstract:INTRODUCTION:Idiopathic pulmonary fibrosis (IPF) is an age-associated, progressive, and irreversible fatal interstitial lung disease. Although many drugs have failed in clinical trials, these failures improved the understanding of the pathogenesis of IPF. Currently, there are two drugs approved for IPF that slow the pr...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1554054
更新日期:2019-01-01 00:00:00
abstract::Leukotriene B(4) (LTB(4)) is a lipid inflammatory mediator derived from membrane phospholipids by the sequential actions of cytosolic phospholipase A2 (PLA2), 5-lipoxygenase (5-LO) and leukotriene A(4) (LTA(4)) hydrolase. Several inflammatory diseases, including asthma, chronic obstructive pulmonary disease, arthritis...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.12.1909
更新日期:2007-12-01 00:00:00
abstract:INTRODUCTION:Currently, there is no cure available for the hereditary neurodegenerative disease proximal spinal muscular atrophy (SMA), which is the number one genetic killer in early childhood. However, growing knowledge of SMA pathophysiology has opened new avenues for potential therapeutic interventions. AREAS COVE...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1038341
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:The salivary gland (SG) in primary Sjögren's syndrome (pSS) is characterized by its lack of function (hyposalivation) and lymphocytic invasion. Small-molecule inhibitors (SMIs) are a new class of drugs, whose diminutive size permits diffusion into cells. SMIs targeting components of the immune system are e...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1631796
更新日期:2019-07-01 00:00:00
abstract::Recombinant toxins constitute a new modality for the treatment of cancer, since they target cells displaying specific surface-receptors or antigens. They are fusion proteins, which contain toxin and ligand regions, and are produced in Escherichia coli. The ligand may be a growth factor or a fragment of an antibody, an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.9.1405
更新日期:1998-09-01 00:00:00
abstract:INTRODUCTION:We carried out a screen for small molecule selective inhibitors of eukaryotic DNA polymerases (pols). Dehydroaltenusin, isolated from a fungus (Alternaria tenuis), was found to be a specific inhibitor of pol α. AREAS COVERED:We succeeded in chemically synthesizing dehydroaltenusin along with five analogs....
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.619977
更新日期:2011-11-01 00:00:00
abstract::The discovery of peroxisome proliferator-activated receptor gamma (PPARgamma) as the molecular target for antidiabetic thiazolidinediones has heralded a new era in the approach to understanding the pathophysiology of insulin resistance and its relationship to cardiovascular disease. However, the subsequent discovery o...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.11.1859
更新日期:1999-11-01 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:INTRODUCTION:In 2010, about 8.8 million new cases of tuberculosis were recorded and 1.1 million people died of tuberculosis worldwide. Although numbers are in decrease since 2006, tuberculosis still represents a global issue and a major public health threat, due to appearance of multidrug-resistant and extensively drug...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.724397
更新日期:2012-12-01 00:00:00
abstract::The tremendous increase in the global prevalence of Type 2 diabetes (T2D) and its conglomeration of metabolic disorders has dramatically intensified the search for innovative therapies to fight this emerging epidemic. Over the last decade, the family of nuclear receptors, especially the peroxisome proliferator-activat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.7.763
更新日期:2006-07-01 00:00:00
abstract::Endothelin (ET) is a pivotal physiological regulator of blood pressure through its effects on blood vessels, heart, lung and kidneys, and the ET system can be overactive in disorders such as pulmonary hypertension, heart failure and renal disease. Such observations stimulated interest among scientists and pharmaceutic...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.11.1419
更新日期:2004-11-01 00:00:00
abstract:INTRODUCTION:Inhibitors against the PD-1/PD-L1 pathway are revolutionizing the treatment and management of malignancies. AREAS COVERED:We summarize our current understanding of the function of PD-1, its role in immune evasion, the clinical data available that support the use of PD-1 antagonist in Hodgkin and non-Hodgk...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1416091
更新日期:2018-01-01 00:00:00
abstract::Intravenous antihypertensive agents are used in clinical situations in which the immediate, precise control of blood pressure is a clinical necessity. Clevidipine is a new, vascular-selective, dihyrdopyridine Ca(2+) channel blocker, which exerts its hemodynamic effects through selective arterial vasodilation without e...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.9.1449
更新日期:2007-09-01 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
abstract:INTRODUCTION:Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-β), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on wh...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2021.1868432
更新日期:2021-01-04 00:00:00
abstract:INTRODUCTION:Although the combination of an anti-CD20 monoclonal antibody and chemotherapy has widely improved survival of patients with B-cell lymphoma, the disease still relapses. A better understanding of the biology of lymphomas has highlighted the role of the cell of origin in response to treatment and outcome. Le...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1208170
更新日期:2016-09-01 00:00:00
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 pharmaceutica...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.5.555
更新日期:1997-05-01 00:00:00
abstract::Clinical trials of several platelet glycoprotein (GP) IIb/IIIa receptor inhibitors have demonstrated an unequivocal benefit of this potent antithrombotic therapy in high-risk patients with acute coronary syndromes (ACS) as well as in those undergoing percutaneous coronary intervention. In all of these major trials, ho...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.9.1567
更新日期:2003-09-01 00:00:00
abstract:INTRODUCTION:Gut-specific homing is mainly mediated by the expression of MAdCAM-1 on endothelial cells. An increase in MAdCAM-1 expression has been shown in patients with inflammatory bowel disease (IBD). Areas covered: PF-00547659 is a fully human monoclonal antibody (mAb) toward MAdCAM-1 on endothelial cells, blockin...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1494722
更新日期:2018-07-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The evolution of targeted therapies is dependent upon identification of cellular moieties that can be pharmacologically modulated. As one such example, the serine-threonine kinase Akt was identified nearly two decades ago. Since then, its role in mediating multiple signaling cascades (ultimately...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.520701
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:Peritoneal carcinomatosis (PC) is a challenging consequence of certain malignancies, associated with a poor prognosis and limited treatment options. Generally, PC has been treated similarly to metastatic cancers of the primary tumor, but associated with worse outcomes when compared to other sites of metastat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780902939151
更新日期:2009-07-01 00:00:00
abstract:INTRODUCTION:Compounds that inhibit or modulate γ-secretase, the pivotal enzyme which generates β-amyloid (Aβ), are potential therapeutics for Alzheimer's disease (AD). AREAS COVERED:This article briefly reviews the profile of γ-secretase inhibitors that have reached the clinic and discusses the clinical issues surrou...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.550572
更新日期:2011-03-01 00:00:00
abstract::Ovarian cancer leads to more fatalities than any other form of gynaecological cancer in North America and Europe. Over the last 30 years survival figures have improved somewhat due to improvements in diagnosis, surgery and chemotherapy. Despite these advances, the majority of patients will die from their disease, with...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.9.1715
更新日期:2001-09-01 00:00:00
abstract::Recently there have been considerable advances made in the treatment of multiple sclerosis. For the first time since its initial clinical description in the 1800s, there are now available several medications which unequivocally exert favourable clinical effects through the lowering of the biological activity of the hu...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.4.655
更新日期:2000-04-01 00:00:00
abstract::Vasopressin (AVP) is a cyclic nonapeptide hormone that exhibits many physiological effects including free water reabsorption, vasoconstriction, cellular proliferation and adrenocorticotrophic hormone (ACTH) secretion. In a healthy organism, AVP plays an important role in the homeostasis of fluid osmolality and volume ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.10.5.825
更新日期:2001-05-01 00:00:00
abstract::Gossypol has received significant attention as a result of its potential therapeutic application as a male antifertility agent. Furthermore, recent research examining the biological activity of gossypol has revealed a number of other promising lines of enquiry. These have focused on the antitumour, antiviral and antio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.11.1419
更新日期:2005-11-01 00:00:00
abstract::Clinical trials showing the benefits of reducing the effects of TNF- alpha in rheumatoid arthritis have highlighted the key role of the cytokine TNF- alpha in this inflammatory condition. A new approach to reducing the effects of TNF- alpha is to decrease its synthesis by inhibiting TNF- alpha converting enzyme with G...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.11.7.1003
更新日期:2002-07-01 00:00:00
abstract::After thousands of years of interest the last few decades have seen a huge increase in our knowledge of the cannabinoids and their mode of action. Their potential as medical therapeutics has long been known. However, very real concerns over their safety and efficacy have lead to caution and suspicion when applying the...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.10.1365
更新日期:2002-10-01 00:00:00
abstract:INTRODUCTION:The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) mainly comprise polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF, primary or post-PV/ET). Therapy in PV and ET focuses on minimizing thrombosis and bleeding risk, while in MF, prolongation of survival is an ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1250882
更新日期:2016-12-01 00:00:00