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 preferred bioactivity outline and alternative bioactive molecules at an early stage. A number of in silico methods have been explored extensively in order to facilitate the investigation of individual target agents and to propose a selective drug. A different, progressively more significant field which is used to predict the bioactivity of chemical compounds is the data mining method. Some of the previously mentioned methods have been investigated for multi-target drug design (MTDD) to find drug leads interact simultaneously with multiple targets. Several cheminformatics methods and structure-based approaches try to extract information from units working cooperatively in a biomolecular system to fulfill their task. To dominate the difficulties of the experimental specification of ligand-target structures, rational methods, namely molecular docking, SAR and QSAR are vital substitutes to obtain knowledge for each structure in atomic insight. These procedures are logically successful for the prediction of binding affinity and have shown promising potential in facilitating MTDD. Here, we review some of the important features of the multi-target therapeutics discoveries using the computational approach, highlighting the SAR, QSAR, docking and pharmacophore methods to discover interactions between drug-target that could be leveraged for curative benefits. A summary of each, followed by examples of its applications in drug design has been provided. Computational efficiency of each method has been represented according to its main strengths and limitations.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Abdolmaleki A,Ghasemi JB,Ghasemi Fdoi
10.2174/1389450117666160101120822subject
Has Abstractpub_date
2017-01-01 00:00:00pages
556-575issue
5eissn
1389-4501issn
1873-5592pii
CDT-EPUB-72844journal_volume
18pub_type
杂志文章,评审abstract::The sphingomyelin (SM) pathway is an ubiquitous and evolutionarily conserved signaling system in which ceramide (CA), generated from SM by the action of various isoforms of sphingomyelinases (SMases) functions as an important second messenger. Recent evidence suggests that branching pathways of sphingolipid metabolism...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450003349272
更新日期:2000-09-01 00:00:00
abstract::Treatment with anti-cancer agents in most cases ultimately results in apoptotic cell death of the target tumor cells. Unfortunately, tumor cells can develop multidrug resistance, e.g., by a reduced propensity to engage in apoptosis by which they become insensitive to multiple chemotherapeutics. Ceramide. the central m...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450043345452
更新日期:2004-05-01 00:00:00
abstract::Transport molecules can significantly affect the pharmacodynamics and pharmacokinetics of drugs. An important transport molecule, the 170 kDa P-glycoprotein (Pgp), is constitutively expressed at several organ sites in the human body. Pgp is expressed at the blood-brain barrier, in the kidneys, liver, intestines and in...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006778019264
更新日期:2006-08-01 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 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::A group of oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas (e.g. hippocampus, medulla oblongata and spinal cord) control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids (N-methyl-...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450033347190
更新日期:2003-01-01 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::Inflammation is the most common pathology in many orthopedic diseases, such as: rheumatoid arthritis (RA), osteoarthritis (OA) and other reasons caused osteolysis. The leading factor of inflammation was considered as the differentiation of monocyte and the polarization of macrophage. However, cytokines and different c...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450120666191015211737
更新日期:2020-01-01 00:00:00
abstract::There exists an immediate need to develop novel medications for the treatment of mood disorders such as bipolar disorder and depression. Initial interest in glycogen synthase kinase-3 (GSK-3) as a target for the treatment of mood disorders arose from the finding that the mood stabilizing drug lithium directly inhibite...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450110607011399
更新日期:2006-11-01 00:00:00
abstract::Atherosclerosis is now widely appreciated to represent a chronic inflammatory reaction of the vascular wall in response to dyslipidemia and endothelial distress involving the inflammatory recruitment of leukocytes and the activation of resident vascular cells. The proliferative response of smooth muscle cells critical...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010791591377
更新日期:2010-08-01 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::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::The hedgehog signal transduction network is a critical regulator of metazoan development. Inappropriate activation of this network is implicated in several different cancers, including breast. Genetic evidence in mice as well as molecular biological studies in human cells clearly indicate that activated signaling can ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010792006753
更新日期:2010-09-01 00:00:00
abstract::Resveratrol (3,4',5 tri-hydroxystilbene) is a phytoalexin produced in hudge amount in grapevine skin in response to infection by Bothrytis cinerea. This production of resveratrol blocks the proliferation of the pathogen, thereby acting as a natural antibiotic. Numerous studies have reported interesting properties of t...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006776359331
更新日期:2006-04-01 00:00:00
abstract::The fibrinolytic system consists of a balance between rates of plasminogen activation and fibrin degradation, both of which are finely regulated by spatio-temporal mechanisms. Three distinct inhibitors of the fibrinolytic system that differently regulate these two steps are plasminogen activator inhibitor type-1 (PAI-...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666190715102510
更新日期:2019-01-01 00:00:00
abstract::The prevalence of periodontitis is around 20-50% of global population. If not treated, it can cause of tooth loss. Periodontal treatment aims at preserving the patient's teeth from various methods, including infection control and restoring lost periodontal tissue. The periodontium has great biological regenerative pot...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121999201105152639
更新日期:2020-11-05 00:00:00
abstract::One approach to identify new drugs with antimicrobial activities is to screen large libraries of molecules directly for their capacity to block the growth of bacterial or fungal monocultures. A more relevant way to assess both a product's efficacy and its potential cytotoxicity is undoubtedly to use an in vivo infecti...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011795677854
更新日期:2011-06-01 00:00:00
abstract::Hypertriglyceridaemia is associated with insulin resistance, hypertension, obesity and diabetes. The management of hypertriglyceridaemia and atherogenic dyslipidaemias increasingly involves the use of several drugs for different aspects of the metabolic syndrome. This review highlights the agents for treatment of bloo...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009787846380
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:Different clinical studies have given inconsistent results on whether the use of antipsychotics increases the risk of thromboembolism. In this paper, we reviewed all relevant literature to provide suggestions for clinical diagnosis and treatment. METHODS:PubMed, Web of Science, EMBASE, MEDLINE, Cochrane and...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200422084414
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::Oxysterols are pleiotropic messengers interacting with multiple receptor systems. One of the cognate receptors for oxysterols is EBI2, a G protein-coupled receptor highly expressed in the cells of the immune system. Here we discuss the receptor's role in the adapted immunity and inflammation as well as the receptor's ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160217123042
更新日期:2016-01-01 00:00:00
abstract::Thrombus formation at a site of arterial injury (eg, rupture of an atherosclerotic plaque in a carotid artery), a crucial step in the pathogenesis of cerebral ischemia, is initiated by the adhesion of platelets to the arterial wall. In vivo, activated platelets release adenosine diphosphate (ADP), whose binding to the...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010790711987
更新日期:2010-03-01 00:00:00
abstract::PDZ domains play an essential role in a number of cellular processes by facilitating protein scaffolding and assembly of protein complexes. These domains consist of 80 to 90 amino acids and are found to recognize short C-terminal sequences of target proteins. Protein complex formation between PDZ target molecules can ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666141219120125
更新日期:2015-01-01 00:00:00
abstract::Rituximab has demonstrated a major effect in B-cell lymphoma and in a wide range of autoimmune disorders. Unfortunately, the blood-brain-barrier excludes the disorders restricted to the central nervous system (CNS) from the action of rituximab. The progressive phase of multiple sclerosis (MS) is a prototypical CNS aut...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141029234644
更新日期:2014-01-01 00:00:00
abstract::Anticancer peptide (ACP) is a kind of small peptides that can kill cancer cells without damaging normal cells. In recent years, ACP has been pre-clinically used for cancer treatment. Therefore, accurate identification of ACPs will promote their clinical applications. In contrast to labor-intensive experimental techniq...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666180801121548
更新日期:2019-01-01 00:00:00
abstract::Novel anti-vasculature strategies that are emerging for the treatment of cancer and for the inhibition of angiogenesis may be a promising new tool for the adjuvant therapy of malignant tumours. Over the last fifteen years, several reports have been published concerning the relationship between tumour progression and a...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009789577954
更新日期:2009-10-01 00:00:00
abstract::The understanding of the neurobiological processes leading to major depressive disorder (MDD) is an active field of research in the scientific community. For years, the alteration of monoamine neurotransmission, in particular serotonin (5-HT), has been considered the most significant pathophysiological mechanism of th...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990154
更新日期:2013-05-01 00:00:00
abstract::Dysbiosis has been repeatedly observed in inflammatory bowel disease (IBD) and is now recognized as an essential factor in the gut inflammatory process. IBD is a significant burden to health-care systems, mainly due to treatment-related costs. Available treatments have several limitations: up to 30% of patients are pr...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200602125507
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:The incidence of inflammatory bowel disease (IBD) continues to rise worldwide and despite the advances on pharmacotherapy, the etiopathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) remains underexplained. In this context, the migratory waves of the last decades created a challenging setting to...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666201119142045
更新日期:2020-11-19 00:00:00
abstract::Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010790980367
更新日期:2010-04-01 00:00:00