Abstract:
:Abnormal regulation of the ubiquitin-proteasome system (UPS) has been known to be involved in the pathogenesis of a variety of human diseases. A number of studies have focused on the identification of small modifiers for the UPS. Even though the proteasome inhibitor Bortezomib (Velcade®) has been approved for the therapy of multiple myeloma and mantle cell lymphoma, there are still no DUB inhibitors endorsed for clinical usage. Since deubiquitinating enzymes (DUBs) are becoming as a new class of modifiers in the UPS, potential drugs that target specific DUBs have been investigated with the development of experimental technologies for screening small inhibitor molecules. However, the molecular mechanisms of these molecules are poorly understood. In order to design and develop specific small inhibitor molecules for specific DUBs, identification of specific substrates and molecular structures for each DUB is required. Here, we review structures, substrates, and small inhibitor molecules of DUBs identified up to date, providing a clear rationale for the development of novel small inhibitor molecules of DUBs for cancer.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Lim KH,Baek KHdoi
10.2174/1381612811319220013subject
Has Abstractpub_date
2013-01-01 00:00:00pages
4039-52issue
22eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20121123-1journal_volume
19pub_type
杂志文章,评审abstract::The review describes key aspects of the synthesis and biological activities of conjugates of oligonucleotides and their analogues with synthetic peptides, in particular aimed towards gene silencing applications. The common methods of synthesis of oligonucleotide-peptide conjugates (OPCs) and PNA-peptide conjugates (PP...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774580769
更新日期:2005-01-01 00:00:00
abstract::Chronic pain is a widespread healthcare problem affecting not only the patient but in many ways all the society. Chronic pain is a disease itself that endures for a long period of time and it is resistant to the majority of medical treatments that provide modest improvements in pain and minimum improvements in physica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140314150634
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:There is a strong rationale for usage of anti-angiogenic agents in epithelial ovarian cancer. Bevacizumab is the most widely investigated anti-VEGF agent and has shown promising results in recent clinical trials. OBJECTIVE:To review the rationale and usage of bevacizumab in advanced epithelial ovarian cance...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212802002689
更新日期:2012-01-01 00:00:00
abstract::Inflammation is part of an important mechanism triggered by the innate immune response that rapidly responds to invading microorganisms and tissue injury. One important elicitor of the inflammatory response is the Gram-negative bacteria component lipopolysaccharide (LPS), which induces the activation of innate immune ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990036
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:The last few decades have witnessed enormous advancements in the field of Pharmaceutical drug, design and delivery. One of the recent developments is the advent of 3DP technology. It has earlier been successfully employed in fields like aerospace, architecture, tissue engineering, biomedical research, medica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181130163027
更新日期:2018-01-01 00:00:00
abstract::Sex-dependent differences are frequently observed in the biological and behavioural effects of substances of abuse, including cannabis. We recently demonstrated a modulating effect of sex and oestrous cycle on cannabinoid-taking and seeking behaviours. Here, we investigated the influence of sex and oestrogen in the re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990430
更新日期:2014-01-01 00:00:00
abstract::Philosophers have been trying to solve the mind-body problem for hundreds of years. Consciousness is the core of this problem: How do subjective conscious sensations, perceptions, feelings, and thoughts arise out of objective physical brain activities? How is this subjective conscious world in causal interaction with ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Although medications should only be prescribed in pregnancy if benefits to the mother outweigh the risk to the fetus, drug use in pregnancy especially prescribed and over-the-counter analgesics, is very common. OBJECTIVE:The objective of this review is to present an update on known changes in analgesic disp...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170825123754
更新日期:2017-01-01 00:00:00
abstract::Free energy simulations are a powerful tool to study molecular recognition. The most rigorous variants can provide in depth understanding for a particular system, but are not suited for high throughput application to large libraries of compounds. Related, but less expensive methods are increasingly popular, including ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319230008
更新日期:2013-01-01 00:00:00
abstract::A large body of evidence on brain development and ageing has revealed that inflammatory processes profoundly affect brain functions during life span of mammalians, including humans. Activation of innate immune mechanisms leading to pro-inflammatory cytokine up-regulation is involved in devastating and disabling human ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794519147
更新日期:2010-01-01 00:00:00
abstract::Head and neck cancer refers to a group of malignancies that affects the epithelium of the upper aereodigestive tract, primarily the lip and mouth, pharynx and larynx. Head and neck cancer is strongly associated with tobacco smoking, alcohol consumption and betel nut chewing, and indeed a reduction in the exposure to t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803307608
更新日期:2012-01-01 00:00:00
abstract::DNA methyltransferase (DNMT) and histone deacetylase are key enzymes mediating the epigenetic regulation of gene expression. DNA hypermethylation and/or histone deacetylation in promoter regions is often associated with downregulation or silencing of transcription. Epigenetic silencing of tumor suppressor genes plays ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990527
更新日期:2014-01-01 00:00:00
abstract::After years of pre-clinical and clinical testing monoclonal antibodies (mAbs) finally offer new therapeutic choices for patients with haematological and solid malignancies both as unconjugated antibody and as vectors to target radionuclides in radioimmunotherapy (RIT). In recent years some of the most exciting clinica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399257
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Bevacizumab (BVZ) is a recombinant humanized antibody that inhibits the vascular endothelial growth factor A (VEGFA) and is used for the treatment of various types of cancer. BVZ is primarily given by the intravenous drip (I.V.), which often leads to low efficacy and various side effects. There...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190306164157
更新日期:2019-01-01 00:00:00
abstract::Catheter ablation for rhythm control in atrial fibrillation has been recognized as an established treatment. Patients with atrial fibrillation suffer from an increased risk of thromboembolic events. Long-term stroke risk and mortality have been shown to be reduced after catheter ablation, still the procedure per se is...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161205115101
更新日期:2017-01-01 00:00:00
abstract::Stem cell therapy heralds a new chapter in cardiovascular regenerative medicine. Cardiovascular implants are often used in both surgery and interventional cardiology. Cardiovascular stents are utilized in percutaneous coronary interventions (PCI), and are classified as either bare metal stents (BMS) or drug-eluting st...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794455058
更新日期:2010-01-01 00:00:00
abstract::Large doses of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are used to treat several diseases including hypertriglyceridemia in humans. Modest levels of EPA and DHA may be obtained from food, particularly from fatty fish. This review presents the literature examining the differences ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789909665
更新日期:2009-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is marked by cognitive dysfunctions and existence of neuropathological hallmarks such as amyloid plaques, and neurofibrillary tangles. It has been observed that a persistent immune response in the brain has appeared as another neuropathological hall...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200531151004
更新日期:2020-05-31 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::Evasion of apoptosis, the cell's intrinsic death program, is a hallmark of human cancers including neuroblastoma. Also, failure to undergo apoptosis may cause treatment resistance, since the cytotoxic activity of anticancer therapies commonly used in the clinic, e.g. chemotherapy, gamma-irradiation or immunotherapy, i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787315846
更新日期:2009-01-01 00:00:00
abstract::Peroxynitrite, the product of the reaction between nitric oxide and superoxide, is spontaneouly formed within most mammalian cells under physiological conditions. Initial work addressing the pathophysiology of peroxynitrite afforded the generally accepted notion that this compound would be the long-term neurotoxic nit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043452910
更新日期:2004-01-01 00:00:00
abstract::Free energy perturbation (FEP) theory coupled to molecular dynamics (MD) or Monte Carlo (MC) statistical mechanics offers a theoretically precise method for determining the free energy differences of related biological inhibitors. Traditionally requiring extensive computational resources and expertise, it is only rece...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799436421
更新日期:2012-01-01 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:BACKGROUND:Buccal delivery is an alluring course of organization for fundamental medication conveyance and it leads direct access to the systemic flow through the interior jugular vein sidesteps drugs from the hepatic first-pass digestion gives high bioavailability. OBJECTIVE:This article aims at buccal medication con...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200614182013
更新日期:2020-01-01 00:00:00
abstract::Sulphur mustard (SM; (2, 2'-dichloroethylsulfide)) was used for the first time in 1917, during the World War I. SM mainly induces DNA damage, oxidative stress, and inflammation. This compound injures the respiratory system, eyes, skin and the endocrine, gastrointestinal, and hematopoietic systems. However, due to the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180903112218
更新日期:2018-01-01 00:00:00
abstract::Drug-induced photosensitivity of the skin is drawing increasing attention. In past few decades, photosensitivity has been reported with an array of drugs, and is now recognized as a noteworthy medical problem by clinicians, regulatory authorities and pharmaceutical industry. The photosensitivity is of two types i.e., ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151209151408
更新日期:2016-01-01 00:00:00
abstract::Pituitary adenylyl cyclase activating polypeptide (PACAP) is a neuropeptide with great neuroprotective effects and remarkable therapeutic potential. PACAP activates several cellular pathways to exert its protective effects. Emerging evidence shows that PACAP can modify the levels and activity of cell cycle components ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181127102311
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal disease, including heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large scale clinical trials of patients with or without diabet...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201103122813
更新日期:2020-11-03 00:00:00
abstract::Infections are the most common inflammatory triggers and acute and chronic infections have been associated with the development and progression of atherosclerotic disease raising interest in the infectious hypothesis of atherosclerosis. Pathogens have been identified in atherosclerotic plaques and large epidemiologica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after experiencing trauma. Actual therapies do not help majority of patients with PTSD. Moreover, extinguished fear memories usually reappear in the individuals when exposed to trauma cues. New drugs to reduce the impact of conditioned cues in ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150710145250
更新日期:2015-01-01 00:00:00