Abstract:
:Drug design based on the structure of specific enzymes playing a role in carcinogenesis, e.g. tyrosine kinases, has been successful at identifying novel effective anticancer drugs. In contrast, no success has been achieved in drug design attempts, in which transcription factors or DNA-transcription factor complexes involved in the pathogenesis of human neoplasms were targeted. This failure is likely to be due to the fact that the mechanism of transcription regulation is probably too complex and still too inadequately understood to be a suitable target for drug design. It seems plausible that the high selectivity of some human tumors to some DNA-interactive anticancer drugs, e.g. cisplatin, is related to an effect on the transcription of genes that are crucial for those tumors. In this article we propose that some natural products have evolutionarily evolved to exert highly specialized functions, including modulation of the transcriptional regulation of specific genes. We discuss in detail the marine natural product Yondelis (Trabectedin, ET-743) that is effective against some soft tissue sarcoma, possibly because it interferes with the aberrant transcription mechanism in these tumors. In addition we highlight the existing evidence that many different natural products are effective inhibitors of NF-kB, a transcription factor that plays a crucial role in inflammation and cancer, indicating that some of these compounds might possess antitumor properties. We propose that large-scale characterization of natural products acting as potential modulators of gene transcription is a realistic and attractive approach to discover compounds therapeutically effective against neoplastic diseases characterized by specific aberrations of transcriptional regulation.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
D'Incalci M,Brunelli D,Marangon E,Simone M,Tavecchio M,Gescher A,Mantovani Rdoi
10.2174/138161207781757097subject
Has Abstractpub_date
2007-01-01 00:00:00pages
2744-50issue
27eissn
1381-6128issn
1873-4286journal_volume
13pub_type
杂志文章,评审abstract::An important goal of biomedical research is to translate basic research findings into practical clinical implementation. Despite the advances in the technology used in drug discovery, the development of drugs for central nervous system diseases remains challenging. The failure rate for new drugs targeting important ce...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200224112534
更新日期:2020-01-01 00:00:00
abstract::Syncytin-1 is a protein coded by a human endogenous retrovirus (HERV) gene of the HERV-W family (HERVWE1). Syncytin- 1 mediates formation of syncytiotrophoblasts through fusion of cytotrophoblasts, a hallmark of terminal differentiation of placental trophoblast linage. Syncytin-1 also possesses nonfusogenic functions ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990541
更新日期:2014-01-01 00:00:00
abstract::Oxidative stress is often considered as a causative factor in carcinogenesis. In addition, current knowledge recognizes oxidative stress as a mechanism by which various cancer therapies act against cancer. To ameliorate the side effects of cancer therapy, many of the patients suffering from cancer are subject to adjuv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140826152822
更新日期:2014-01-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are a group of aquired hematopoietic disorders characterized by ineffective hematopoiesis, and increased risk of progression of acute myeloid leukemia. For a long period of time, the standard therapy for MDS was hematopoietic stem cell transplantation, however DNA methyltransferase inhi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811209023204
更新日期:2012-01-01 00:00:00
abstract::Heat shock proteins (HSPs) are involved in a number of cellular processes, including cell cycle, growth, and survival, apoptosis, stress responses, angiogenesis, and oncogenesis. Among the characterized HSPs, the molecular chaperone HSP90 has emerged as an exciting molecular target for cancer therapy since its discove...
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::Doxorubicin has been a constituent of antitumor drug protocols for a broad spectrum of cancers for more than two decades. Side effects and resistance continue to be important limitations. Drug targets responsible for both side effects and anti-tumor activity are cell membrane receptors, cell membrane lipids, nucleic a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1998-06-01 00:00:00
abstract::Acute kidney injury (AKI) is relatively common in patients undergoing transcatheter aortic valve implantation (TAVI) and has been associated with increased mortality and worse outcomes. The administration of iodinated contrast media in an elderly population with increased rates of chronic kidney injury and heart failu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151208120522
更新日期:2016-01-01 00:00:00
abstract::Somatostatin is a tetradeca peptide hormone produced by many different endocrine cells throughout the body. It is also present in both the central and peripheral nervous system. The peptide has many different moods of action including inhibition of hormone secretion and influence on gastrointestinal motility. Somatost...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 00:00:00
abstract::Atherosclerosis is still the principal cause of morbidity and mortality in Western countries and although a significant progress has been made in the understanding of its pathophysiology, the determinants of atherosclerotic plaque instability are still poorly understood. The endothelium plays a pivotal role for the de...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780831239
更新日期:2007-01-01 00:00:00
abstract::Regeneration of bone requires the coordinated processes of angiogenesis and osteogenesis. These repair mechanisms are closely linked through both direct cell-cell contact and indirect paracrine signaling among osteoblasts, endothelial cells, and other cell types. The vasculature provides a source of nutrients, oxygen,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319190007
更新日期:2013-01-01 00:00:00
abstract::The clinical presentation of heart disease is different between men and women and this distinction is pivotal for a correct diagnosis and an adequate treatment. However, the definition of symptoms classically associated with heart disease is mainly based on the characteristics of those reported in men. Chest pain or c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211795656927
更新日期:2011-01-01 00:00:00
abstract::ATP-sensitive K+ channels, termed K(ATP) channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolari...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054546879
更新日期:2005-01-01 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:BACKGROUND:Cardiac resynchronization therapy (CRT) is a valuable intracardiac device--based treatment option for a subgroup of patients with advanced heart failure (HF) and QRS prolongation. However, still a significant proportion of patients do not benefit from CRT implantation, labeled as non-responders. OBJECTIVES:...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190621155718
更新日期:2019-01-01 00:00:00
abstract::Inhaled glucocorticoids, also know as corticosteroids (ICS), revolutionized the treatment of asthma by suppressing airways inflammation and ICS therapy now forms the basis of treatment of asthma of all severities. More recently and usually in combination with a long-acting β-agonist (LABA), ICS use has been establishe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161210793797889
更新日期:2010-01-01 00:00:00
abstract::The serotonergic system is involved in pathomechanisms of both epilepsy and neuropathic pain. So far, participation in the epileptogenesis and maintenance of epilepsy was proved for 5-HT1A, 5-HT2C, 5-HT3, 5-HT4 and 5-HT7 receptors as well as 5-HTT serotonin transporter. Depending on the receptor type or its localizati...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666141121114917
更新日期:2015-01-01 00:00:00
abstract::Guanine-rich sequences found in telomeres and oncogene promoters have the ability to form G-quadruplex structures. In this paper we describe the use of a virtual screening assay to search a database of FDA-approved compounds for compounds with the potential to bind G-quadruplex DNA. More than 750 telomerase inhibitors...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612811319120004
更新日期:2013-01-01 00:00:00
abstract::Post-translational modification of histones is a primary mechanism through which epigenetic regulation of DNA transcription does occur. Among these modifications, regulation of histone acetylation state is an important tool to influence gene expression. Epigenetic regulation of neurodevelopment contributes to the stru...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319280003
更新日期:2013-01-01 00:00:00
abstract::Chemotherapy is one of the most frequently employed and reliable treatment options for the management of a variety of cancers. Taxanes (paclitaxel, docetaxel and cabazitaxel) are frequently prescribed to treat breast cancer, hormone refractory prostate cancer, non-small cell lung cancer and ovarian cancer. Most of the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160524144926
更新日期:2016-01-01 00:00:00
abstract::The common mechanism of action of aspirin and the chemically unrelated non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of prostaglandin (PG) production due to interference with the enzymatic activity of cyclooxygenase (COX). These agents have long been used as effective treatments for arthritis. The r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003398753
更新日期:2000-11-01 00:00:00
abstract::Our current understanding of cancer suggests that every tumour has individual features. Approaches to cancer treatment require thorough comprehension of the mechanisms triggering genomic instability and protecting cancer cells from therapeutic treatments. Base excision repair (BER) is a frontline DNA repair system tha...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170710123602
更新日期:2017-01-01 00:00:00
abstract::The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of co...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208799316401
更新日期:2008-01-01 00:00:00
abstract::ADAM (a disintegrin and metalloproteinase) proteins have a predominant role in the protein ectodomain shedding of membrane-bound molecules. ADAMs have emerged as critical regulators of cell-cell signaling during development and homeostasis, and are believed to contribute to pathologies, such as cancer, where their reg...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788682415
更新日期:2009-01-01 00:00:00
abstract::Tocotrienols, components belonging to vitamin E members, are used as potent therapeutics in the treatment of several diseases. Recent studies suggested tocotrienol to have better activity in many situations compared to tocopherols. Tocotrienols have been shown to lower the atherogenic apolipoprotein B and lipoprotein ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796957436
更新日期:2011-01-01 00:00:00
abstract::Schizophrenia is characterised by positive, negative, cognitive, depressive and anxiety symptoms. Over the last decades a number of novel treatment strategies with better clinical efficacy and scope, but with lower side-effect profiles have been developed. These have significantly improved the management and prognosis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150605105215
更新日期:2015-01-01 00:00:00
abstract::The present mini review offers a brief overview on the preparation and modification of gold nanomaterials (AuNMs) designed for biomedical applications, including biosensors, bioimaging, phototherapy and importantly gene/drug delivery. As biocompatibility is a prerequisite for safe pharmaceutical application, the poten...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151210123225
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Clinic resting heart rate (RHR), is one of the cardiovascular parameters more easily measurable. In the general population RHR has been associated with total and cardiovascular mortality and higher rate of vascular events. OBJECTIVE:The case of essential hypertension is in some ways peculiar: in the past de...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170911102711
更新日期:2017-01-01 00:00:00
abstract::P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803251934
更新日期:2012-01-01 00:00:00
abstract::650 millions of adults are obese worldwide - in the US alone, forty percent of the adults are obese. Although the obesity pandemic is constantly expanding at very high costs for health care systems, the currently available options of pharmacotherapy for obesity are rather limited. Despite intensive research efforts, t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190708192630
更新日期:2019-01-01 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