Abstract:
:Improvements in our understanding of the intrinsic aberrancies in cancer cells have enabled the design and development of novel therapeutics that specifically target these changes. Among the many complex cellular pathways and mechanisms which have been unveiled by new molecular techniques, RAS-mediated signal transduction is one met with tremendous research interests. Activation of RAS initiates several signaling cascades, of which the RAS-RAF-MEK-ERK pathway is among the better delineated, and is the main focus of this review. Other cellular consequences of RAS activation including interactions with the RHO-family proteins, the PI3-kinase pathway, and other mitogen activated protein kinase cascades, will be discussed. The intricate balance and coordination of multiple RAS-mediated signals lead to ultimate effects on cell growth, differentiation, cycling and survival. Pharmacological strategies such as analog development, synthesis of small molecule inhibitors, antisense technology, and vaccine therapy have been utilized to intervene with key RAS-signaling proteins, in an attempt to provide rational therapeutic solutions in malignant diseases.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Nottage M,Siu LLdoi
10.2174/1381612023393107subject
Has Abstractpub_date
2002-01-01 00:00:00pages
2231-42issue
25eissn
1381-6128issn
1873-4286journal_volume
8pub_type
杂志文章,评审abstract::P-Glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein that works as an efflux pump and confers multidrug resistance (MDR) in normal tissues and tumors, including nervous tissues and brain tumors. In the developing telencephalon, the endothelial expression of P-gp, and the subcellular localization of the transp...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200318130625
更新日期:2020-01-01 00:00:00
abstract::Angiogenic eye disease is among the most common causes of blindness worldwide. Current treatment approaches are insufficiently effective and partially associated with significant adverse effects. From an investigational view, the eye provides an ideal setting to observe real-time and serial observations of angiogenesi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367292
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:A substantial part of literature has been centered on sex differences in the clinical aspects of ischemic heart disease (IHD). Many reports have documented differences in the presentation and risk profile between women and men. Such differences drive sex-related inequalities in the referral and treatment of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160311115344
更新日期:2016-01-01 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
abstract::The HIV/AIDS pandemic continues its spread at a rate of over 15,000 new infections every day. Sexual transmission of HIV-1 is the dominant mode of this pandemic spread. For the first time since the disease emerged in the early 1980s, about half the 42 million people now living with HIV/AIDS worldwide are women. Worldw...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043386374
更新日期:2004-01-01 00:00:00
abstract::Deubiquitinating enzymes (DUBs) remove ubiquitin and ubiquitin-like modifications from proteins and they have been known to contribute to processes relevant in microbial infection, such as immune responses pathways. Numerous viral and bacterial DUBs have been identified, and activities of several host DUBs are known t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319180008
更新日期:2013-01-01 00:00:00
abstract::A wide range of peptides and polypeptides can be appended to either the N- or C-terminus of G protein-coupled receptors without disrupting substantially ligand binding and signal transduction. Following fusion of fluorescent proteins, reporter gene constructs or G protein alpha subunits to the C-terminal tail of a rec...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384295
更新日期:2004-01-01 00:00:00
abstract::The analysis of enantiorecognition processes involves the detection of enantiomeric species as well as the study of chiral discrimination mechanisms. In both fields Nuclear Magnetic Resonance (NMR) spectroscopy plays a fundamental role, providing several tools, based on the use of suitable chiral auxiliaries, for obse...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778743628
更新日期:2006-01-01 00:00:00
abstract::Drug designing targeting protein-protein interactions is challenging. Because structural elucidation and computational analysis have revealed the importance of hot spot residues in stabilizing these interactions, there have been on-going efforts to develop drugs which bind the hot spots and out-compete the native prot...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990073
更新日期:2014-01-01 00:00:00
abstract:: ...
journal_title:Current pharmaceutical design
pub_type: 社论
doi:10.2174/138161282518190822153931
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND & AIMS:Nowadays, the world is facing a common problem that the population aging process is accelerating. How to delay metabolic disorders in middle-aged and elderly people, has become a hot scientific and social issue worthy of attention. The liver plays an important role in lipid metabolism, and abnormal li...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200605111232
更新日期:2020-01-01 00:00:00
abstract::Most heterosexual women want to reduce the risk of acquiring a sexually transmitted infection; many also want to control their fertility. Several chemical agents have been proposed to dramatically slow the spread of HIV infections. Ideally, vaginal microbicides, with or without contraceptive properties, should be safe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774580705
更新日期:2005-01-01 00:00:00
abstract::Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788168146
更新日期:2009-01-01 00:00:00
abstract::The term endozepines designates a family of astroglia-secreted proteins including the diazepambinding inhibitor (DBI) and its processing products, which have been originally isolated and characterized as endogenous ligands of benzodiazepine receptors. It is now clearly established that the octadecaneuropeptide ODN (DB...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181112111746
更新日期:2018-01-01 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:BACKGROUND:Endothelial dysfunction is commonly present in estrogen-deficient states, e.g., after menopause. In the search for alternatives to hormone replacement therapy (HRT), treatments based on phytoestrogens or in non-hormonal mechanisms have been under evaluation. OBJECTIVE:Here we aim to present an overview of i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200331084338
更新日期:2020-01-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of hepatic dysfunction and is highly correlated with components of the metabolic syndrome such as obesity, insulin resistance and type 2 diabetes. Among others, nutritional factors, physical inactivity, genetic variants and visceral obesity h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791208938
更新日期:2010-06-01 00:00:00
abstract::The last decades have witnessed an explosion in studies of the role of amyloid-β (Aβ) in the progress of the neurodegenerative disorder Alzheimer's disease (AD) and it is now widely accepted that Aβ is related to the pathogenesis of AD. For example, studies have shown that Aβ is neurotoxic and that the neurotoxicity o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797416039
更新日期:2011-01-01 00:00:00
abstract::Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients. The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399077
更新日期:2000-10-01 00:00:00
abstract::Abdominal aortic aneurysm (AAA) is a devastating disease associated with high prevalence of death due to aortic rupture. Currently the therapy is restricted to surgical procedures to prevent aortic rupture, which in turn has a risk for postoperative mortality. There are no proven pharmacological therapies available to...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150826093318
更新日期:2015-01-01 00:00:00
abstract::Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170720113216
更新日期:2017-11-16 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::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::Arterial thromboembolism is a sudden obstruction of arterial blood flow caused by dislodgment of a blood clot from the site of its formation. Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major risk factor for arterial thromboembolism in clinical practice. Most of AF-related arterial thromboembo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793563400
更新日期:2010-01-01 00:00:00
abstract::Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393233
更新日期:2002-01-01 00:00:00
abstract::First generation drug-eluting stents (DES) have significantly improved the treatment options for patients with symptomatic coronary artery disease by decreasing rates of acute vessel closure and restenosis after percutaneous coronary revascularization procedures. However, early enthusiasm was temperd by reports of lat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794454879
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Vitamin D is involved in the physiological functions of several tissues, however, its deficiency may contribute to the development of various disorders. Recent research has been focusing on the role of vitamin D in the pathogenesis of endometriosis based on the evidence of the presence of vitamin D receptor ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190722095401
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Multi-drug resistant infections are a growing worldwide health concern. There is an urgent need to produce alternative antimicrobial agents. OBJECTIVE:The study aimed to design a new hybrid antimicrobial peptide, and to evaluate its antimicrobial activity alone and in combination with traditional antibiotic...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200128090700
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Medical treatments are used either alone or in combination with assisted reproductive techniques for treatment of infertile patients with hypergonadotropic hypogonadism. A wide range of treatment options such as gonadotropins, aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs) and the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201102110456
更新日期:2020-11-01 00:00:00
abstract::Hyperuricemia, has been traditionally related to nephrolithiasis and gout. However, it has also been associated with the development of type 2 diabetes mellitus (T2DM) and cardiometabolic and cardiovascular diseases. Pathophysiologically, elevated serum uric acid (SUA) levels may be associated with abnormal lipid and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612827666210104124320
更新日期:2021-01-04 00:00:00