Abstract:
:Insulin-sensitizing thiazolidinediones (TZDs) correct a root cause of type 2 diabetes and potentially other diseases of metabolic dysfunction, including conditions ranging from oncologic, inflammatory, and neurodegenerative diseases. Importantly, compounds with this mode of action can modify disease progression, as opposed to simply mitigating symptoms. However, side effects have limited the use of marketed agents. Moreover, the same and additional issues have prevented development of newer agents, and no new compounds with this mode of action have been approved since 1999. Here we briefly review the drug discovery track record of compounds in the TZD class as well as several classes of compounds that have been designed with substitutes for the TZD ring, while maintaining and/or expanding the ability to directly activate peroxisome proliferator-activated receptor (PPAR) transcription factors. A key discovery that could change the course of drug discovery in this area is a newly identified mitochondrial target for the insulin sensitizers. This has allowed new drug discovery into molecules designed to maintain this mitochondrial interaction while specifically avoiding significant interactions with PPAR receptors. This commentary suggests that a fresh approach could pave the way for a new directed group of therapeutic agents with potential for disease modification of common metabolic disorders.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Colca JR,Tanis SP,McDonald WG,Kletzien RFdoi
10.1517/13543784.2013.839659subject
Has Abstractpub_date
2014-01-01 00:00:00pages
1-7issue
1eissn
1354-3784issn
1744-7658journal_volume
23pub_type
社论,评审abstract::Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world for those patients aged 50 years or older. Neovascular AMD, a subtype characterized by the growth of new, pathologic blood vessels, results in most of the cases of severe and rapid vision loss associated with AMD. A critical ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780902855316
更新日期:2009-05-01 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:INTRODUCTION:Inhaled corticosteroids are the only drugs that effectively suppress the airway inflammation, but they can induce considerable systemic and adverse effects when they are administered chronically at high doses. Consequently, the pharmaceutical industry is still searching for newer entities with an improved ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1078310
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Microtubule stabilizing agents such as taxanes are an integral part of therapy for multiple solid tumors. However, due to limitations of these agents, newer more effective cytotoxic agents are necessary. Ixabepilone, an epothilone B analog, is a novel microtubule stabilizing agent. OBJECTIVE:This review pro...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.3.423
更新日期:2008-03-01 00:00:00
abstract::There is a growing understanding of the central role that platelets play in coronary artery disease. The glycoprotein IIb/IIIa receptor has recently been identified as the final common pathway for platelet aggregation and hence has been the focus of many clinical trials to influence various aspects of coronary artery ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.11.1645
更新日期:2002-11-01 00:00:00
abstract:INTRODUCTION:The significant proportion of gout patients not reaching serum urate levels below 6.0 mg/dL and the debated pathogenicity of hyperuricemia (HU) itself motivate investigators to develop new drugs to decrease uricemia. AREAS COVERED:This review discusses the drugs considered to be in active development from...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1471133
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND:Histone deacetylases (HDACs), which target histones as well as non-histone proteins as substrates, have the potential to regulate aberrant gene expression and restore normal growth control in malignancies. OBJECTIVE:This review provides an updated summary of preclinical and clinical experience with the oral...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.8.1247
更新日期:2008-08-01 00:00:00
abstract:INTRODUCTION:Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of D...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1360274
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Studies in vitro and in vivo have identified several peptides that are potentially useful in treating systemic lupus erythematosus (SLE). The rationale for their use lies in the cost-effective production, high potency, target selectivity, low toxicity, and a peculiar mechanism of action that is mainly base...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1777983
更新日期:2020-08-01 00:00:00
abstract::Cyclin-dependent protein kinases (CDKs) are key regulators of the cell division cycle, whose various checkpoints proliferating cells must traverse. Since CDK deregulation, either through direct or indirect means, is found in most cancer cells, pharmacological CDK inhibition has become an attractive strategy towards me...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.6.955
更新日期:2003-06-01 00:00:00
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::Fatty acid synthase (FASN) is the enzyme that catalyzes the de novo synthesis of fatty acids in cells. Because of the strong expression in many cancers, FASN is an attractive and tractable target for therapeutic intervention. The discovery and development of pharmacologic agents that block FASN activity highlight the ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.11.1817
更新日期:2007-11-01 00:00:00
abstract::In order to improve therapy and increase the quality of life for diabetic patients, it has been of significant interest to develop rapid-acting insulin preparations that mimic the physiological meal-time profile of insulin more closely than soluble human insulin. Insulin aspart (B28Asp human insulin) is a novel rapid-...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.9.1431
更新日期:1999-09-01 00:00:00
abstract::Parasitic infections are widespread in developing countries and frequently associated with immunocompromised patients in developed countries. Consequently, such infections are responsible for a significant amount of human mortality, morbidity and economic hardship. A growing consensus has identified the urgent need fo...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.8.957
更新日期:2005-08-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Aspirin, an irreversible inhibitor of thromboxane A(2) production, in combination with clopidogrel, an inhibitor of PY(12) ADP platelet receptors, represents the current standard-of-care of antiplatelet therapy for patients with acute coronary syndrome and those undergoing percutaneous coronary ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.521741
更新日期:2010-12-01 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: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::Gaucher disease (GD) is an inborn error of glycosphingolipid metabolism, associated with multisystemic manifestations resulting from the lysosomal accumulation of an incompletely degraded material (glucosylceramide) within cells of monocyte/macrophage lineage. In the majority of GD patients with non-neurological invol...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.2.273
更新日期:2003-02-01 00:00:00
abstract:INTRODUCTION:Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two complications of diabetes that cause visual loss and blindness. Laser photo-coagulation in the past was used to prevent progression of disease to these advanced stages. Advances in pathophysiologic understanding of DME an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1201062
更新日期:2016-09-01 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::Since the introduction of the first through the skin (TTS) therapeutic in 1980, a total of 34 TTS products have been marketed and numerous drugs have been tested by more than 50 commercial organisations for their suitability for TTS delivery. Most of the agents which have been tested have had low molecular weights, du...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.12.1887
更新日期:1997-12-01 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: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::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:About 185,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). Currently, the most successful HCV infection antiviral therapies reduce the chance of progression towards the advanced phases of the hepatopathy (liver cirrhosis, hepatocellular carcinoma and death). Recently, however...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1059820
更新日期:2015-01-01 00:00:00
abstract::The vasopressin system is complex and interacts with the central nervous, cardiovascular, renal, and hematological systems. Vasopressin plays an important role in the control of blood osmolarity and vascular tone, but is also involved in many other physiological events, which are mediated mainly via three types of vas...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903066764
更新日期:2009-08-01 00:00:00
abstract::New therapies targeting critical elements of the cell cycle open novel and attractive avenues for the treatment of cancer patients. At present, the number of clinical trials that are registered with the European Organization for Research and Treatment of Cancer (EORTC) and with the US National Cancer Institute, which ...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
doi:10.1517/13543784.2012.691163
更新日期:2012-08-01 00:00:00
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:INTRODUCTION:Ewing sarcoma family tumors (ESFT) are a group of aggressive diseases, characterized histologically by small, round, blue cells and genetically by translocation involving EWS and ETS partner genes. The current treatment of localized Ewing sarcoma (ES) requires a multi-disciplinary approach, including multi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2016.1168398
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Polidocanol is a liquid surfactant having endothelial cell lytic properties. In the form of a controlled, dispensed microfoam it is administered endovenously as a sclerosing agent in the treatment of varicose veins. OBJECTIVE:This review summarizes efficacy of polidocanol endovenous microfoam sclerotherapy ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903376163
更新日期:2009-12-01 00:00:00