Abstract:
INTRODUCTION:Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to improve clinical outcomes. Since lethal toxin and edema toxin (LT and ET) make central contributions to the pathogenesis of B. anthracis, these have been major targets in this effort. AREAS COVERED:Here, the authors review different investigative biopharmaceuticals that have been recently identified for their therapeutic potential as inhibitors of LT or ET. Among these inhibitors are two antibody preparations that have been included in the Strategic National Stockpile (SNS) and several more that have reached Phase I testing. Presently, however, many of these candidate agents have only been studied in vitro and very few tested in bacteria-challenged models. EXPERT OPINION:Although a large number of drugs have been identified as potential therapeutic inhibitors of LT and ET, in most cases their testing has been limited. The use of the two SNS antibody therapies during a large-scale exposure to B. anthracis will be difficult. Further testing and development of agents with oral bioavailability and relatively long shelf lives should be a focus for future research.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Ohanjanian L,Remy KE,Li Y,Cui X,Eichacker PQdoi
10.1517/13543784.2015.1041587subject
Has Abstractpub_date
2015-01-01 00:00:00pages
851-65issue
7eissn
1354-3784issn
1744-7658journal_volume
24pub_type
杂志文章,评审abstract::Increasing evidence suggests an important role for autocrine/paracrine prolactin in breast and prostate cancers and other disease states. Prolactin production in these extrapituitary sites is not governed by dopamine agonists, a finding that has spurred the production of prolactin receptor antagonists. This review foc...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.10.1257
更新日期:2006-10-01 00:00:00
abstract::Background: We aimed to estimate population-based trends in the prevalence of coexisting type 2 diabetes (T2D) and suspected nonalcoholic fatty liver disease (NAFLD) and pioglitazone use among U.S. adults.Research design and methods: We conducted a cross-sectional analysis of the National Health and Nutrition Examinat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1704731
更新日期:2020-02-01 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:Peripheral arterial disease (PAD) is a manifestation, and marker of severity, of a generalized atherosclerotic process. Antiplatelet therapy is recommended to prevent cardiovascular events but much of the evidence to support this is drawn from studies on older drugs. AREAS COVERED:In this review, the auth...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.974803
更新日期:2014-12-01 00:00:00
abstract:INTRODUCTION:Dyslipidemia is one of the most important risk factors for cardiovascular disease. Insufficient reduction in LDL-C from existing therapies in patients at high risk of atherogenic cardiovascular disease is an unmet clinical need. Circulating PCSK9 causes hypercholesterolemia by reducing LDL receptors in hep...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1442435
更新日期:2018-03-01 00:00:00
abstract::The role of nerve growth factor in stimulating cholinergic function, loss of which is a cardinal feature in Alzheimer's disease, has been documented for many years from preclinical animal model studies. This anabolic growth factor has been delivered into the forebrain of patients with mild Alzheimer's disease using tr...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.7.913
更新日期:2005-07-01 00:00:00
abstract:INTRODUCTION:Stroke is the second leading cause of death worldwide and the leading cause of adult neurological disability. Despite advances in stroke unit care, and increasing use of thrombolysis, there remains an urgent need for safe and effective treatments for acute ischaemic stroke. However, this is against a backd...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1020110
更新日期:2015-05-01 00:00:00
abstract::Inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) has an established role in the treatment of advanced non-small cell lung cancer. The first-generation EGFR inhibitors erlotinib and gefitinib have been approved for treatment in the second- and third-line setting. Second-generation ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780902762843
更新日期:2009-03-01 00:00:00
abstract::Considerable progress has been made with tyrosine kinase inhibitors. After long and sustained efforts, several tyrosine kinase inhibitors with convincing in vivo experimental antitumour properties such as CP-358,774, ZD 1839, CEP-751 are entering Phase I clinical trials. Significant in vivo experimental antitumour act...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.6.771
更新日期:1997-06-01 00:00:00
abstract::BCR-ABL, a constitutively active tyrosine kinase, causes chronic myeloid leukaemia (CML). Rational development of drugs targeting BCR-ABL has significantly improved the treatment of CML. Imatinib (a BCR-ABL tyrosine kinase inhibitor) produces haematological and cytogenetic remissions across all phases of CML and is th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.5.679
更新日期:2007-05-01 00:00:00
abstract::TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.6.1383
更新日期:2000-06-01 00:00:00
abstract::Colorectal cancer is one of the most common cancers worldwide. Through well-designed clinical trials, advances have been made in the treatment of localised and advanced colorectal cancer. It has been established that 6 months of 5-fluorouracil-based chemotherapy will improve overall survival in patients with stage III...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.6.871
更新日期:2002-06-01 00:00:00
abstract:INTRODUCTION:Signal transducer and activator of transcription 3 (STAT3) controls a key signaling pathway in the development of many malignant diseases. Several genetic studies have proven its central role in the regulation of apoptosis, proliferation, angiogenesis and immune responses making it an attractive target for...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.601739
更新日期:2011-09-01 00:00:00
abstract:INTRODUCTION:Due to improvements in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), several target drugs have been and are being developed. One of the possible targets in SLE is co-stimulation between antigen-presenting cells and T cells. Abatacept is a co-stimulation moderator approved for...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2016.1154943
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Acute decompensated heart failure (ADHF) is associated with increased hospitalization rates and high in-hospital mortality, and has emerged as a major public health problem over the past decade. In recent years, several new drugs and therapeutic approaches have failed to reduce short- and long-term morbidity...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780902922660
更新日期:2009-06-01 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:BACKGROUND:Age-related macular degeneration is the leading cause of blindness among elderly individuals in industrialized countries. New drugs and advanced concepts for the treatment of dry AMD (dAMD) are needed. A new approach is the application of intravenous infusions of prostaglandin E1. OBJECTIVE:The aim of this ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1517/13543784.2013.794782
更新日期:2013-07-01 00:00:00
abstract:INTRODUCTION:The N-methyl-d-aspartate receptor-ionophore complex plays a key role in learning and memory and has efficacy in animals and humans with affective disorders. GLYX-13 is an N-methyl-d-aspartate receptor (NMDAR) glycine-site functional partial agonist and cognitive enhancer that also shows rapid antidepressan...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.852536
更新日期:2014-02-01 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::Restenosis, the re-narrowing of the lumen of the coronary artery, in the months following a successful percutaneous balloon angioplasty or stenting, remains the main limitation to percutaneous coronary revascularisation. Serial intravascular ultrasound studies have shown that restenosis after conventional balloon angi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.11.2555
更新日期:2000-11-01 00:00:00
abstract:INTRODUCTION:Vascular-disrupting agents (VDAs) are a new class of oncology drugs, which specifically target established tumor neovasculature and have a relatively low toxicity profile. VDAs generally have non-overlapping side effects when concomitantly used with conventional cytotoxics. Several members of the VDA class...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.759557
更新日期:2013-03-01 00:00:00
abstract:INTRODUCTION:Posttraumatic stress disorder (PTSD) is a prevalent, chronic and disabling anxiety disorder that may develop following exposure to a traumatic event. There is currently no effective pharmacotherapy for PTSD and therefore the discovery of novel, evidence-based treatments is particularly important. This revi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1020109
更新日期:2015-05-01 00:00:00
abstract::Aripiprazole has made a significant contribution to the treatment of schizophrenia and related disorders with an improved safety and tolerability profile, which has been attributed to its unique pharmacological profile. It has been claimed that partial agonism of the dopamine D(2) and 5-HT(1A) receptors and antagonism...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.6.771
更新日期:2007-06-01 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:INTRODUCTION:Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity. Although many currently available treatment regimens are effective, poor symptom control and refractory severe disease still represent major unmet needs. In the last years, numerous molecular therapeutic targets that inte...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1212838
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::All of the glucose-lowering agents available today for the treatment of diabetes resulted from the in vivo antidiabetic drug discovery approach. This is not surprising given the limited understanding of the biochemical basis of diabetes. With new developments in the elucidation of the biochemistry and physiology of di...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.6.987
更新日期:1998-06-01 00:00:00
abstract::Obesity shortens life expectancy and is a risk factor for hypertension and Type 2 diabetes. When added to the standard chow of Sprague-Dawley or Otsuka Long-Evans Tokushima Fatty rats, alpha-lipoic acid (0.5% weight/weight) reduced body weight and food intake. Alpha-lipoic acid also increased whole-body energy expendi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.12.1641
更新日期:2004-12-01 00:00:00
abstract::Growth hormone-insensitivity syndrome (GHIS) is usually caused by mutations in the growth hormone receptor. Recombinant IGF-I has been used to treat GHIS either alone (mecasermin) or in combination with IGF-binding protein (IGFBP)-3 (mecasermin rinfabate). IGF-I increases the growth velocity of children with IGF defic...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.4.409
更新日期:2006-04-01 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