Abstract:
:Crohn's disease (CD) and ulcerative colitis (UC), two chronic and relapsing inflammatory bowel diseases (IBD), are supposed to develop in genetically-predisposed individuals as a result of an excessive immune mucosal response directed against normal components of the gut microbiota. There is also evidence that defects in counter-regulatory mechanisms play a major role in the pathogenesis of IBD. One such a defect involves TGF-β1, a cytokine produced by multiple cells types and able to inhibit pathogenic responses in the gut. In both CD and UC, TGF-β1 is highly produced but unable to signal through the TGF-β receptor-associated Smad pathway and suppress production of inflammatory molecules. Abrogation of TGF-β1 activity has been related to Smad7, an intracellular protein that binds to TGF-β receptor and inhibits TGF-β1-driven Smad-dependent signalling. Indeed, silencing of Smad7 with a specific antisense oligonucleotide restores TGF-β1/Smad signalling, thereby down-regulating inflammatory cytokine production and ameliorating experimental colitis in mice. Altogether these observations led to the development of an oral pharmaceutical compound containing the specific Smad7 antisense oligonucleotide (herein termed GED0301), which seems to be safe and well tolerated in CD patients. In this article we summarize the data supporting the pathogenic role of Smad7 in IBD and discuss the recent results of the use of GED0301 in CD.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Marafini I,Zorzi F,Codazza S,Pallone F,Monteleone Gdoi
10.2174/13894501113149990157subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1400-4issue
12eissn
1389-4501issn
1873-5592pii
CDT-EPUB-20130313-1journal_volume
14pub_type
杂志文章,评审abstract:BACKGROUND:It becomes increasingly evident that the SARS-CoV-2 infection is not limited to the respiratory system. In addition to being a target of the virus, the kidney also seems to have a substantial influence on the outcomes of the disease. METHODS:Data was obtained by a comprehensive and non-systematic search in ...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121999201013151300
更新日期:2021-01-01 00:00:00
abstract::Trypanosomes and Leishmaniae are the agents of several important parasitic diseases threatening hundreds of million human beings worldwide. As they diverged early in evolution, they display original molecular characteristics. These peculiarities are each defining putative specific targets for anti-parasitic drugs. Tra...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008786786064
更新日期:2008-11-01 00:00:00
abstract::The etiopathogenesis of Crohn's disease (CD) and ulcerative Colitis (UC), the two major forms of inflammatory bowel disease (IBD), is still unknown. Although the exact cause and mechanisms of both IBD have yet to be completely understood, it is widely accepted that both CD and UC result from an inappropriate immune re...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008784221170
更新日期:2008-05-01 00:00:00
abstract:AIMS:The aim of this study is to provide an overview of several emerging anti-diabetic molecules. BACKGROUND:Diabetes is a complex metabolic disorder involving the dysregulation of glucose homeostasis at various levels. Insulin, which is produced by β-pancreatic cells, is a chief regulator of glucose metabolism, regul...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450120666191031104653
更新日期:2020-01-01 00:00:00
abstract::Lung cancer kills approximately 1.3 million citizens in the world annually. The tyrosine kinase inhibitors (TKI) erlotinib and gefitinib are effective anti-tumor agents especially in lung cancer patients with epidermal growth factor receptor (EGFR) mutations. The goal is to increase the potency of TKI in lung cancer p...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150107153609
更新日期:2016-01-01 00:00:00
abstract::Memories associated with substance use disorders, or substance-associated cues increase the likelihood of craving and relapse during abstinence. There is a growing consensus that manipulation of synaptic plasticity may reduce the strength of substance abuse-related memories. On the biological front, there are new insi...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450118666170622092824
更新日期:2019-01-01 00:00:00
abstract::Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properti...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141107105456
更新日期:2014-01-01 00:00:00
abstract::Multi-target drugs against particular multiple targets get better protection, resistance profiles and curative influence by cooperative rules of a key beneficial target with resistance behavior and compensatory elements. Computational techniques can assist us in the efforts to design novel drugs (ligands) with a prefe...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160101120822
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666180115164103
更新日期:2018-01-01 00:00:00
abstract::Epigenetic modifications ensure the maintenance of normal cellular functions, and their dysregulation is frequently found in many disease states, including cancer. Nowadays, the most studied epigenetic dysregulation associated with tumorigenesis, cancer progression and metastasis refers to the variations in DNA methyl...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200325093104
更新日期:2020-01-01 00:00:00
abstract::Epithelia are the layers of cells that form barriers between external milieu and underlying tissues and thus, are important components of most organs of the body. Epithelial layers of organs, such as the lung, are exposed to various challenges resulting in frequent injury. Epithelial wound healing represents an import...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006776818719
更新日期:2006-05-01 00:00:00
abstract::With the development of modern assisted reproductive technology(ART), the treatment of infertility and the pregnant outcome by ART have been significantly improved. However, implantation failure, particularly the unexplained repeated implantation failure (RIF), is still the unsolved and principal problem to affect the...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111314080006
更新日期:2013-07-01 00:00:00
abstract::Antiphospholipid syndrome (APS) is characterized by a combination of clinical features consisted of thrombotic or pregnancy-related events and autoimmune antiphospholipid antibodies. In the 1998 International Consensus Preliminary Criteria, APS is defined by the concomitant presence of these clinical features and labo...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450054545999
更新日期:2005-08-01 00:00:00
abstract::The emergency of responsive drug delivery systems has contributed to the reduced cytotoxicity, the improved permeability in tissues and extended circulation time of the active drug. Of particular, enzyme-responsive nanoplatforms have attracted a lot due to the specificity and efficiency of an enzyme-catalyzed reaction...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450122666210114095614
更新日期:2021-01-13 00:00:00
abstract::The contribution of proteases to developmental, physiological and pathological processes has been well accepted. Cleavage of matrix proteins is a key requirement for cell migration and remodeling of the extracellular environment. The constant process of matrix turnover is dependent on the delicate balance between degr...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008785909365
更新日期:2008-10-01 00:00:00
abstract::According to international guidelines, treatment of cervical cancer (CC) consists of surgery in early stages and of chemoradiation in locally advanced disease. Metastatic disease is usually treated with palliative chemotherapeutic regimens, but cytostatic drugs present significant side effects and show limited activit...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141010145547
更新日期:2014-01-01 00:00:00
abstract::Family C of G-protein coupled receptors (GPCRs) from humans is constituted by eight metabotropic glutamate (mGlu(1-8)) receptors, two heterodimeric gamma-aminobutyric acid(B) (GABA(B)) receptors, a calcium-sensing receptor (CaR), three taste (T1R) receptors, a promiscuous L-alpha-amino acid receptor (GPRC6A), and five...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007779315614
更新日期:2007-01-01 00:00:00
abstract::Retinal neovascularization and macular edema are central features of diabetic retinopathy, a major cause of blindness in working age adults. The currently established treatment for diabetic retinopathy targets the vascular pathology by laser photocoagulation. This approach is associated with significant adverse effect...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450054021981
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:The plant milk thistle and silymarin has been traditionally used as a natural remedy for the treatment of various ailments including neurological disorders such as Alzheimer's and Parkinson's disease and cerebral ischemia for over 2000 years. OBJECTIVE:In this article we review the neuroprotective effects o...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666161227125121
更新日期:2017-01-01 00:00:00
abstract::The Wnt signaling pathway has important functions in development, tissue homeostasis, and regeneration. Deregulation of canonical Wnt/beta-catenin signaling is frequently found in various human cancers, particularly in colorectal cancer, and non-canonical Wnt signaling pathways also have been implicated in neoplasia. ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008784911769
更新日期:2008-07-01 00:00:00
abstract::The liver is essential for the control of glucose and lipid metabolism. Excessive accumulation of fat in the liver disturbs its function and leads to the development of fatty liver diseases. The nonalcoholic fatty liver disease (NAFLD) is a common type of fatty liver disease found in patients who have not consumed sig...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150325231015
更新日期:2015-01-01 00:00:00
abstract::Radiation-induced myelosuppression remains a rate-limiting factor of radiotherapy and chemotherapy. Therefore, hematological targets of radiation damage are of great significance for radiation oncology and normal tissue injury and protection. Protection of hematopoietic stem and progenitor cells is pivotal. In order t...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111009011375
更新日期:2010-11-01 00:00:00
abstract::Thrombomodulin (TM) is a type 1 membrane bound glycoprotein that has a C-type lectin domain at its Nterminus, 6 copies of the epidermal growth factor-like (EGF) motif and serine/threonine rich domain carrying a glycosoaminoglycan external to the membrane. TM binds thrombin changing thrombin's substrate specificity fro...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012799424606
更新日期:2012-03-01 00:00:00
abstract::Galectin-1 (Gal1) was the first identified member of the galectin family of beta-galactosidase-binding proteins. Gal1 has important roles in processes fundamental to growth and survival of an organism, including cell adhesion, cell proliferation and apoptosis, and is expressed in many tissues, including the nervous sy...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450054021864
更新日期:2005-06-01 00:00:00
abstract:OBJECTIVE:To investigated the use of mixed treatment comparison (MTC) meta-analysis models to summarize results from randomized clinical trials (RCTs) on approved pharmacological treatments for neovascular age-related macular degeneration (AMD). METHODS:The number of patients with visual loss or visual gain of 3 or mo...
journal_title:Current drug targets
pub_type: 杂志文章,meta分析,评审
doi:10.2174/138945011794182665
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:Endometriosis (EMS) is a gynecological disease defined by the translocation and growth of endometrial tissue in other tissues or organs outside the uterus. Its clinical manifestations are dysmenorrhea, irregular menstruation, and even infertility. Although EMS is a benign disease, it has the characteristics ...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200228112344
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1573399811666150615145409
更新日期:2018-01-01 00:00:00
abstract::The popular use of antioxidative vitamins illustrates the growing awareness of oxidative stress as an important hazard to our health and as an important factor in the ageing process. Superoxide radicals and superoxide-derived reactive oxygen species (ROS) are constantly formed in most cells and tissues. To ensure that...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450110607011505
更新日期:2006-11-01 00:00:00
abstract::HIV-1 replicates by infecting new target cells either as cell-free viral particle or, much more efficiently, via cell-to-cell viral transmission. Cell-mediated viral spread, in which the infected cell directly transfers the viral particles to target cells via cell-cell contacts, in vitro is up to three orders of magni...
journal_title:Current drug targets
pub_type: 杂志文章
doi:
更新日期:2015-08-25 00:00:00
abstract::The adenosine pathway is a powerful evolutionarily selected mechanism aimed at a fine modulation of inflammatory responses and protection of tissues from injuries. Adenosine exerts its modulatory effects via interaction with G protein-coupled receptors, designated as A(1), A(2A), A(2B) and A(3). In this regard, extrac...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012800564095
更新日期:2012-06-01 00:00:00