Abstract:
:Inhibition of fatty acid oxidation is well recognized as a potentially effective mechanism for controlling glycemia in non-insulin-dependent diabetes mellitus (NIDDM). However, a direct targeting of inhibition of the intramitochondrial beta-oxidation pathway or an indirect modulation of fatty acid oxidation by inhibition of substrate release from adipose stores has been fraught with lack of efficacy, unacceptable side-effects or both. Focus has therefore recently been directed towards the carnitine palmitoyltransferase (CPT) system, a three-component system necessary for the transfer of long-chain fatty acids into the intramitochondrial matrix. This article will briefly review the background for fatty acid oxidation inhibition in NIDDM and then focus on the progress in the biological understanding and drug discovery targeting of the CPT system for the treatment of NIDDM. Based upon the review, it is concluded that mechanism-based hepatic and myocardial toxicities in normal animals and a potential for a lack of human efficacy may pose insurmountable hurdles for the development of CPT inhibitors for the treatment of NIDDM.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Anderson RCsubject
Has Abstractpub_date
1998-02-01 00:00:00pages
1-16issue
1eissn
1381-6128issn
1873-4286journal_volume
4pub_type
杂志文章,评审abstract::Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival. Since cancer cells have frequently disrupted different cell death pathways that promote their survival, mitochondria may be key organelles to promote cell death in cancer cel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796904803
更新日期:2011-01-01 00:00:00
abstract::Cardiac ischemia, followed by reperfusion, often results in the development of cardiac contractile dysfunction that limits the recovery prognosis of patients. The current goal of pharmacological therapy in the course of ischemic heart disease is to improve the oxygen supply/demand ratio for the heart. Cardiac contract...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990556
更新日期:2014-01-01 00:00:00
abstract::G-quadruplexes have found increasing potential in applications such as molecular therapeutics, diagnostics, and sensing. As a consequence, small molecules capable of selectively detecting G-quadruplexes have received significant attention in recent literature. Our review here addresses representative advances in the d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799958314
更新日期:2012-01-01 00:00:00
abstract::Transpeptidation reactions result in the formation of new peptide bonds and this can occur between two separate peptides or within the one peptide. These reactions are catalyzed by enzymes and when the N- and C-terminus of the one peptide are joined it results in the formation of cyclic proteins. Cyclization via head-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798999410
更新日期:2011-12-01 00:00:00
abstract::Increased plasma levels of both leptin and C reactive protein (CRP) have been reported in a number of conditions, including obesity, and have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk; interestingly these two biomarkers appear to be able to reciprocally regulate their...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990016
更新日期:2014-01-01 00:00:00
abstract::Human heart has endogenous regenerative capability; however, the intrinsic repair mechanism is not sufficient to overcome the impact placed by adverse pathological conditions, such as myocardial infarction (MI). In such circumstances, the damaged tissue initiates a series of remodeling process which results in the det...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150302153138
更新日期:2015-01-01 00:00:00
abstract::Erectile dysfunction (ED) has multifactor pathogenesis, with neurological, vascular, endocrinological and psychogenic components described. However, about 50-85% of ED population report the presence of one or more comorbidities i.e. hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair endothel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778343046
更新日期:2006-01-01 00:00:00
abstract::Food proteins contain latent biofunctional peptide sequences within their primary structures which may have the ability to exert a physiological response in vivo. A large range of biofunctional peptides have been isolated from food proteins including opioid, immunomodulatory, antimicrobial, mineral binding, growth and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780363068
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Neglected tropical diseases (NTDs) represent a serious problem in a number of countries around the world and especially in Africa and South America, affecting mostly the poor population which has limited access to the healthcare system. The drugs currently used for the treatment of NTDs are dated many decade...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201210115340
更新日期:2020-12-09 00:00:00
abstract:BACKGROUND:Anticoagulation in patients with pulmonary embolism. OBJECTIVE:To identify how non-vitamin K antagonist oral anticoagulants are associated with multiple outcomes in patients with pulmonary embolism. METHODS:We performed a systematic search of systematic reviews via multiple electronic databases from incept...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200506114450
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:The prevalence of adrenal hyperandrogenism (AH), as defined by increased circulating dehydroepiandrosterone-sulfate (DHEAS) levels, ranges from 15 to 45% in women with polycystic ovary syndrome (PCOS). METHODS:The aim of this review is to update the pathogenesis and consequences of AH in PCOS, from molecula...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160720150625
更新日期:2016-01-01 00:00:00
abstract::Many, if not all, chronic medical, neurodegenerative and neuroprogressive illnesses are characterised by chronic immune activation, oxidative and nitrosative stress (O&NS) and systemic inflammation. These factors, notably elevated pro-inflammatory cytokines, activate indoleamine 2,3-dioxygenase (IDO) leading to an upr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151215102420
更新日期:2016-01-01 00:00:00
abstract::Prion diseases are fatal neurodegenerative disorders associated with conformational conversion of the cellular prion protein (PrP(C)) into an isoform designated PrP(Sc). The pathogenic mechanism that links this conformational distortion with the development of prion diseases is unknown. PrP(C) is a GPI-anchored cell s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777698873
更新日期:2006-01-01 00:00:00
abstract::Approximately half of patients with schizophrenia have a lifetime diagnosis of substance abuse disorders. These dual diagnosis patients are more likely to have poorer outcomes, including more severe psychiatric symptoms with increased hospitalizations, higher utilization of services and frequent homelessness. Assessme...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384114
更新日期:2004-01-01 00:00:00
abstract::Adverse reactions after iodinate contrast media (ICM) administration have been observed, which can be classified as immediate (i.e., occurring within one hour after administration) and delayed or non-immediate (i.e., occurring more than one hour after administration). Even though the incidence of ICM adverse reactions...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778193999
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:There is an increasing interest from the pharmaceutical and food industry in natural antioxidant and bioactive compounds derived from plants as substitutes for synthetic compounds. The genus Allium is one of the largest genera, with more than 900 species, including important cultivated and wild species, havi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200203145851
更新日期:2020-01-01 00:00:00
abstract::In this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex formation may involve titratable groups with unusual pKa's and that protonation states frequently change from unbound to bound states. These protonation ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319230004
更新日期:2013-01-01 00:00:00
abstract::Δ(9)-tetrahydrocannabinol (Δ(9)-THC) is the main compound of the Cannabis Sativa responsible for most of the effects of the plant. Another major constituent is cannabidiol (CBD), formerly regarded to be devoid of pharmacological activity. However, laboratory rodents and human studies have shown that this cannabinoid i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802884681
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Breast cancer is the most frequently diagnosed malignancy in women worldwide. Breast cancer tends to metastasize to bone. Around 70% of the breast cancer patients eventually develop bone metastasis. After the bone invasion, metastatic cells disrupt the balance between osteoblastic and osteoclastic activities...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180619165728
更新日期:2018-01-01 00:00:00
abstract::The acidic amino acid L-glutamate acts as both a primary excitatory neurotransmitter and a potential neurotoxin within the mammalian central nervous system. Functionally juxtaposed between these neurophysiological and pathological actions are an assorted group of integral membrane transporter proteins that rapidly and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-05-01 00:00:00
abstract::The receptor for urokinase plasminogen activator (uPAR) is required in hematopoietic stem/progenitor cells (HSC, HPC) mobilization in the mouse. Indeed, uPAR Ko mice are deficient both in retention and mobilization of HSC and HPC, because uPAR causes their retention in the BM through its interaction with the α4β1 inte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211796718206
更新日期:2011-01-01 00:00:00
abstract::Hepatitis C virus (HCV) infections are a serious viral health problem globally, causing liver cirrhosis and inflammation that can develop to hepatocellular carcinoma and death. Since the HCV NS3/4A protease complex cleaves the scissile peptide bond in the viral encoded polypeptide to release the non-structural protein...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990632
更新日期:2014-01-01 00:00:00
abstract::The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated Cl- channel whose major function is to facilitate epithelial fluid secretion. Loss-of-function mutations in CFTR cause the genetic disease cystic fibrosis. CFTR is required for transepithelial fluid transport in certain secretor...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990321
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Blood flow assessment is essential to fully understand cardiovascular function in disease pathologies and for identification of individuals at long-term risk of cardiovascular disease development. Qualitative and quantitative assessments of blood flow by imaging modalities have been limited, and much of the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170317144257
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Familial Hypercholesterolaemia (FH) is an autosomal-dominant genetic disease and represents the most common genetic disorder: heterozygous 1/250 births, homozygous 1/300, 000 births. FH is characterized by high to very high low-density lipoprotein cholesterol (LDL-C), which is the main cause of increased inc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181009105305
更新日期:2018-01-01 00:00:00
abstract::Cyclooxygenase-1 (COX-1) derived eicosanoids promote gastroprotective mucosal defenses and induce platelet aggregation. By sparing COX-1, COX-2 specific inhibitors provide effective anti-inflammatory and analgesic activity while substantially reducing the risk of peptic ulcer disease and GI bleeding compared to dual C...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454018
更新日期:2003-01-01 00:00:00
abstract::Atherosclerosis is an inflammatory vascular disease that is characterized by progressive accumulation of cholesterol in the arterial walls and it is a major cause of cardiovascular disease. Issues related to the side effects of synthetic drugs have in recent times, led to the misuse of drugs, a lack of patient consult...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180911121525
更新日期:2018-01-01 00:00:00
abstract::Many of the most debilitating symptoms for psychiatric disorders such as schizophrenia remain poorly treated. As such, the development of novel treatments is urgently needed. Unfortunately, the costs associated with high failure rates for investigational compounds as they enter clinical trials has led to pharmaceutica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160127113912
更新日期:2016-01-01 00:00:00
abstract::Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing conditions resulting from immune system activity in a genetically predisposed individual. IBD is based on progressive damage to the inflamed gut tissue. As its pathogenesis remains unknown, recent accumu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200406081920
更新日期:2020-01-01 00:00:00
abstract::Although the pathogenesis of inflammatory bowel disease (IBD) remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of anti-inflammatory agents, aminosalicylates...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033455035
更新日期:2003-01-01 00:00:00