Abstract:
:Aberrant signaling caused by mutations in the RAS-RAF-MEK-ERK pathway and its upstream activators critically contributes to human tumor development. Strategies, which aim at inhibiting hyperactive signaling molecules, appear conceptually straight forward, but their translation into clinical practice has been hampered by many setbacks. Understanding structure, function and regulation of this intracellular pathway as well as its crosstalk with other signaling activities in the cell will be essential to ensure reasonable usage of new therapeutic possibilities. This review provides an understanding of this signaling cascade as revealed by genetic and biochemical approaches and discusses the existing or arising possibilities to interfere with unphysiological activation in cancer. Signaling aberrations and signal transduction therapies will be discussed exemplary for two types of hematological neoplasia, acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS). In the future understanding the role of tumor stem cells, both as a source of tumor recurrence and tumor heterogeneity, the signals controlling their fate as well as epigenetic changes in cancer will be the next critical steps to further advance the applicability of these novel therapeutic strategies.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Zebisch A,Czernilofsky AP,Keri G,Smigelskaite J,Sill H,Troppmair Jdoi
10.2174/092986707780059670subject
Has Abstractpub_date
2007-01-01 00:00:00pages
601-23issue
5eissn
0929-8673issn
1875-533Xjournal_volume
14pub_type
杂志文章,评审abstract::Evidence indicates that nerve gas toxins operate in ways in addition to inhibition of acetylcholine esterase. Alternative bioactivities are discussed with focus on electron transfer. The main class, including pralidoxime (2-PAM), incorporates conjugated iminium and oxime moieties that are electron affinic. Various phy...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033456314
更新日期:2003-12-01 00:00:00
abstract::Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of di...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170605091546
更新日期:2017-01-01 00:00:00
abstract::Cancer is the world's second leading cause of death after heart diseases, and involves abnormal cell growth at a primary site and the potential to spread to other parts of the body. Tumors are highly heterogeneous and consist of subgroups of cells with distinct characteristics. Of these, the cancer stem cells (CSC) ni...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867327666200320155053
更新日期:2020-03-20 00:00:00
abstract::Since the beginning of the 20th century, important medicinal progress has led medical doctors to think that the end of devastating epidemics has arrived. In 1930, the discovery of sulfamides and penicillin opened a wide area of applications able to fight against bacterial infections. However, almost all antibiotics we...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986705774933470
更新日期:2005-01-01 00:00:00
abstract::Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Two very common neglected tropical diseases are Chagas' disease and leishmaniasis. Chagas' disease is a severe health problem, mainly in Latin America, causing approximately 50000 deaths a year and m...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867325666171201101807
更新日期:2017-01-01 00:00:00
abstract::The identification and characterisation of the isoenzyme cyclooxygenase 2 (COX-2) stimulated investigations to develop efficient non-steroidal anti-inflammatory drugs with reduced side effects compared to standard NSAIDs. This review will focus on the structural features needed to achieve COX-2 selectivity. Five struc...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867003374237
更新日期:2000-11-01 00:00:00
abstract::Tuberculosis (TB) is the leading cause of mortality due to a single infectious agent. The currently used combination drug regimens produce cure rates that exceed 95%, given good patient adherence during the multiple months treatment period. However the recent surge in HIV infections and the synergy between HIV and TB ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708783955509
更新日期:2008-01-01 00:00:00
abstract:: ...
journal_title:Current medicinal chemistry
pub_type: 社论
doi:10.2174/092986732608190516092613
更新日期:2019-01-01 00:00:00
abstract::Pyoverdine is the generic name given to a vast family of fluorescent green-yellowish pigments produced by Pseudomonas species. Pseudomonas aeruginosa is an opportunistic pathogen, particularly infecting humans with compromised natural defenses. These infections result in significantly higher morbidity, longer hospital...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867321666141011194624
更新日期:2015-01-01 00:00:00
abstract::N-BP, rapamycin and its derivatives have been originally developed respectively as anti-resorptive and anti-fungal agents. In fact, in vitro and in vivo experiments demonstrated that these compounds are multi-functional molecules exerting their effects on tumour cell growth and bone remodelling. The major challenge in...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707780831159
更新日期:2007-01-01 00:00:00
abstract::Currently, the long-term usage of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in HIVAIDS patients eventually leads to the development of drug resistance and severe side effect. Therefore, it is imperative to look for the novel NNRTIs with potent and broad spectrum anti-mutant activity that are also safe a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788803231
更新日期:2009-01-01 00:00:00
abstract::Sweat is an alternative biological matrix useful to detect drugs of abuse intake. It is produced by eccrine and apocrine glands originating in the skin dermis and terminating in secretory canals that flow into the skin surface and hair follicles. Since many years it has been demonstrated that endogenous and exogenous ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311320040006
更新日期:2013-01-01 00:00:00
abstract::Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 family, is reported to exhibit a plethora of pleiotropic effects in the heart such as cytoprotective, pro-proliferative and pro-fibrotic ones. An extensive research has been devoted on proliferative and profibrotic effects of CT-1 on the heart. Thus the presen...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986713804806702
更新日期:2013-01-01 00:00:00
abstract::In modern industrialized societies, people are exposed to thousands of naturally occurring and synthetic chemicals throughout their lifetime. Although certain occupational chemicals are known to be carcinogenic in humans, it has been difficult to definitively determine the adverse health effects of many environmental ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708786242930
更新日期:2008-01-01 00:00:00
abstract::Prothymosin alpha (ProTα) is a highly acidic polypeptide, ubiquitously expressed in almost all mammalian cells and tissues and consisting of 109 amino acids in humans. ProTα is known to act both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier medi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190807145212
更新日期:2020-01-01 00:00:00
abstract::Genito-urinary malignancies (prostate, bladder, renal and testicular cancers) rank high among human tumors with an incidence that varies with age and organ involvement. Prostate cancer is the most commonly detected male cancer followed by bladder and kidney cancers, less frequent in women. Testicular cancer, although ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711797535182
更新日期:2011-01-01 00:00:00
abstract::Melatonin, a tryptophan-derived neurohormone found in animals, plants, and microbes, participates in various biological and physiological functions. Among other properties, numerous in vitro or in vivo studies have reported its therapeutic potential against many parasites, bacteria and viruses. In this concern, melato...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666150827093730
更新日期:2015-01-01 00:00:00
abstract::Diabetic patients have a two- to four-fold increased risk for the development of microvascular (renal, neuronal and retinal) and macrovascular complications. Unfortunately, these complications may develop in both Type 1 and Type 2 diabetic patients even with careful glycaemic, blood pressure and lipid control. With th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706777452515
更新日期:2006-01-01 00:00:00
abstract::β-Aryl-β-amino acids constitute very useful scaffolds able to lead, via various intra-molecular cyclisation reactions, to a great diversity of cyclic derivatives with numerous biological and therapeutic properties. The present article aims at reporting an exhaustive overview of these ring-closure sequences and their a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710793361261
更新日期:2010-01-01 00:00:00
abstract::Neural differentiation of embryonic stem cells (ESC) is considered a promising model to perform in vitro testing for neuroactive and neurotoxic compounds. We studied the potential of a dual reporter murine ESC line to identify bioactive and/or toxic compounds. This line expressed firefly luciferase under the control o...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986713804999330
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Steroid hormones belong to a group of low-molecular weight compounds which are responsible for maintenance of various body functions, thus, their accurate assessment is crucial for evaluation of biosynthetic defects. The development of reliable methods allowing disease diagnosis is essential to improve early...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666171113120810
更新日期:2019-01-01 00:00:00
abstract::Breast cancer is an example of a solid tumour which is well treated in the early stages of disease by surgical excision, but once metastatic spread has occurred, medical therapies (chemotherapy and radiotherapy) are highly toxic, expensive and palliative. It is known that certain tumours exhibit specific patterns of m...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033457944
更新日期:2003-04-01 00:00:00
abstract::Active pharmaceutical ingredients (APIs), frequently delivered to the patient in the solid-state as part of an approved dosage form, can exist in such diverse solid forms as polymorphs, pseudopolymorphs, salts, co-crystals and amorphous solids. Various solid forms often display different mechanical, thermal, physical ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787549299
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170718130408
更新日期:2019-01-01 00:00:00
abstract::The present review aims to provide a complete and comprehensive summary of current literature relevant to oxysterols and related diseases. Oxidation of cholesterol leads to the formation of a large number of oxidized products, generally known as oxysterols. They are intermediates in the biosynthesis of bile acids, ste...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867327666200316142659
更新日期:2021-01-01 00:00:00
abstract::Poly(aminoester) dendrimers are expected to hold great promise as biodegradable nanocarriers for drug delivery due to their advantageous properties allowing their biodegradability, potentially lower toxicity and possibility of diverse chemical conjugations. The synthetic strategies for constructing such dendrimers inc...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311209025011
更新日期:2012-01-01 00:00:00
abstract::Cardiovascular pathologies in the French are not prevalent despite high dietary saturated fat consumption. This is commonly referred to as the "French Paradox" attributing its anti-lipidemic effects to moderate consumption of red wine. Resveratrol, a phytoalexin found in red wine, is currently the focus of intense res...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708784638861
更新日期:2008-01-01 00:00:00
abstract::The chemokine receptor, CXCR4, is a GPCR that transduces signals of its endogenous ligand, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 system plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, etc. This...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707779313499
更新日期:2007-01-01 00:00:00
abstract::Akuammiline alkaloids are a family of monoterpene indole alkaloids of renewed medicinal interest. These bases act as ligands for a heterogeneous group of molecular targets and, consequently, display a wide variety of pharmacological activities. For example, pseudoakuammigine (2) exhibits opioid activity in vivo, echit...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033457016
更新日期:2003-09-01 00:00:00
abstract::It is well accepted that inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is one of high risk factors for colorectal cancer (CRC). This supports the notion that inflammation plays a key role in cancer development. Epidemiologic studies have shown that vitamin D (Vit D) deficiency is ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867323666161202153028
更新日期:2017-01-01 00:00:00