Abstract:
:Preclinical studies suggest that the brain corticotropin-releasing factor (CRF) systems mediate anxiety-like behavioural and somatic responses through actions at the CRF1 receptor. CRF1 antagonists block the anxiogenic-like effects of CRF and stress in animal models. Cerebrospinal fluid levels of CRF are elevated in some anxiety disorders and normalise with effective treatment, further implicating CRF systems as a therapeutic target. Prototypical CRF1 antagonists are highly lipophilic, non-competitive antagonists of peptide ligands. Modification of the chemotype and the identification of novel pharmacophores are yielding more drug-like structures with increased hydrophilicity at physiological pHs. Newer compounds exhibit improved solubility, pharmacokinetic properties, potency and efficacy. Several clinical candidates have entered Phase I/II trials. However, unmet challenges await resolution during further discovery, clinical development and therapeutic application of CRF1 antagonists.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Zorrilla EP,Koob GFdoi
10.1517/13543784.13.7.799subject
Has Abstractpub_date
2004-07-01 00:00:00pages
799-828issue
7eissn
1354-3784issn
1744-7658pii
EID130706journal_volume
13pub_type
杂志文章,评审abstract::Biologically-based skin substitutes have developed as commercial products over the last 5 years. The first generation includes the collagen-based synthetic device, Integra, and Alloderm, which is based on devitalised and cross-linked human dermis. These are used as dermal replacements for third degree burns. Within th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.5.803
更新日期:1998-05-01 00:00:00
abstract::Sitagliptin is a once-daily, orally active, competitive and fully reversible inhibitor of dipeptidyl peptidase 4, the enzyme that is responsible for the rapid degradation of the incretin hormone glucagon-like peptide-1. It is the first in this new class of antihyperglycaemic agents to gain regulatory approval for the ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.4.533
更新日期:2007-04-01 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:INTRODUCTION:Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis. With the emergence of monoclonal antibodies and tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR), several drugs were developed and tested in HNSCC. To date, the monoclonal...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1177022
更新日期:2016-06-01 00:00:00
abstract::Psoriasis is a chronic skin disorder characterised by inflammation producing red, thickened areas with a flaky white build-up. Efalizumab is a humanised monoclonal IgG1 antibody that inhibits the binding of T lymphocytes to endothelial cells and their subsequent migration. In patients suffering from plaque psoriasis, ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.13.5.551
更新日期:2004-05-01 00:00:00
abstract:INTRODUCTION:There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infect...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1005205
更新日期:2015-03-01 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:INTRODUCTION:Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Pharmacological treatment of AD includes Anticholinesterase Inhibitors (AChEIs) for mild-moderate AD, and memantine for severe AD. These drugs provide mainly symptomatic short-term benefits without clearly influencing the progres...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1265504
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Clusterin is a stress-induced cytoprotective chaperone protein, regulated by HSF1, and functions similarly to a small heat-shock protein. Clusterin is expressed in a variety of cancers and associated with broad-spectrum treatment resistance. Custirsen (OGX-011) is a 2'-methoxyethyl modified phosphorothioate ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780802528609
更新日期:2008-12-01 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::Recent advances in the treatment and management of haematological malignancies are due in large part to an improved understanding of the basic biology that drives tumour cell growth and survival. This improved understanding has led to the clinical study and approval of a number of different targeted agents across a nu...
journal_title:Expert opinion on investigational drugs
pub_type:
doi:10.1517/13543784.14.9.1161
更新日期:2005-09-01 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:BACKGROUND:Today, propofol or 2,6-diisopropylphenol is the anesthetic mainly used for monitored anesthetic care sedation and during intravenous anesthesia. The formulation, a lipid macroemulsion, shows several disadvantages. Therefore, during the past years considerable scientific effort has been undertaken to find eit...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903193063
更新日期:2009-10-01 00:00:00
abstract:INTRODUCTION:The addition of monoclonal antibody (mAb) epidermal growth factor receptor (EGFR) inhibitors to classic chemotherapy doublet backbones has improved survival of metastatic colorectal cancer (mCRC). However, the role of triple-drug chemotherapy regimens in combination with an anti-EGFR mAb inhibitor is not y...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1599860
更新日期:2019-05-01 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: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::There is still considerable interest in cephem antibacterial agents. In fact, there are a significant number of patents submitted for this antibacterial class. All the new cephem derivatives, independent of which group they belong to (III to V), possess a 2-amino-5-thiazolyl or a 5-amino-2-thiadiazolyl ring with an ox...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.3.305
更新日期:1997-03-01 00:00:00
abstract::Novel classes of antibiotics that are useful against resistant bacteria are a major need in human medicine. Cationic antimicrobial peptides are utilised as nature's antibiotics, being produced constitutively or in response to infection in virtually every type of organism from plants and insects to man. Thus, these pep...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.2.167
更新日期:1998-02-01 00:00:00
abstract::Proliferative diabetic retinopathy (PDR) demands both more effective and less expensive biologically based treatments. Our understanding of the pathophysiology of the disease is increasing as new biochemical pathways are identified. Most reports emphasize proangiogenic stimuli, with the natural inhibitory elements rec...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.8.1209
更新日期:2007-08-01 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:BACKGROUND:In the past years the bone seeking radiopharmaceutical samarium lexidronam ((153)Sm-EDTMP) has been increasingly used alone or in conjunction with chemotherapy and/or bisphosphonates for the treatment of painful bone metastasis. OBJECTIVE:Its use has been explored in different solid tumours. In this report ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.17.9.1379
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND:Treatment of advanced renal cell carcinoma (RCC) has undergone significant changes over the past 3 years after a long period of relative stagnation. A better understanding of the biology of the tumor led to the discovery of molecular targeted therapies resulting in significant improvement in outcome for this...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.10.1501
更新日期:2008-10-01 00:00:00
abstract:INTRODUCTION:Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth, and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. AREAS COVERED:We ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1513490
更新日期:2018-10-01 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::Atopic dermatitis (AD) is a common inflammatory disease involving the skin and often other organs and systems, mainly respiratory. A definitive general consensus on the AD pathogenesis has not yet been established, however several lines of evidence suggest that T-cells play a crucial role in priming AD early-stage les...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.1.49
更新日期:2001-01-01 00:00:00
abstract::This paper gives an overview of the available pharmacological and clinical data of a new class of anticancer drugs which act by binding DNA in the minor groove, comprising cyclopropylpyrrolo-indole (CC-1065) derivatives and Distamycin derivatives. The emphasis of this review is placed on the distinctive mode of action...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.7.875
更新日期:1997-07-01 00:00:00
abstract::New bolus fibrinolytic agents derived from the recombinant human tissue plasminogen activator (t-PA) have emerged as a new means of dissolution of the occlusive thrombosis associated with acute myocardial infarction. Lanoteplase is a fibrinolytic drug derived from t-PA by deleting its fibronectin finger-like and epide...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.11.2689
更新日期:2000-11-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Curcumin has been investigated in preclinical and translational stroke models because of its pleiotropic 'neuroprotective' activities. Since curcumin has poor blood-brain barrier (BBB) penetration following acute administration, creative medicinal chemistry has been used to modify the parent cur...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.542410
更新日期:2011-01-01 00:00:00
abstract::Many peptides are synthesised and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it has become increasingly evident that they also influence eating behaviour. Peptide YY (PYY) is released postprandially from gastrointestinal ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.5.647
更新日期:2005-05-01 00:00:00
abstract:INTRODUCTION:In the last decade, concerns have been raised around the use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in chronic kidney disease (CKD) patients, especially when given at high doses. Moreover, treatment with ESA is expensive. AREAS COVERED:We searched PubMed for original articles, re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1493455
更新日期:2018-07-01 00:00:00