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 from procoagulant and pro-inflammatory to anti-coagulant and anti-inflammatory because of the activation of protein C (PC) and thrombin-activatable fibrinolysis inhibitor (TAFI). Thrombin's anion binding site 1 binds to TM's EGF domains 5 and 6. EGF4 is required for PC activation and EGF3 and 4 for TAFI activation in addition to EGF56. The X-ray structure of thrombin bound to TM has been solved and shows few major alterations in the active site of thrombin. The lectin domain can bind high mobility group box protein 1 (HMGB1) and a sugar, Lewis Y. TM's lectin domain behaves as an antagonist to HMGB1 endowing it with intrinsic anti-inflammatory activity. Treatment of dendritic cells with TM converts them from immunogenic to tolerogenic. TM is necessary for maintenance of pregnancy as well as prevention of coagulation throughout life. Soluble TM has been developed as an anticoagulant possessing favorable pharmacokinetics that has been approved for treatment of disseminated intravascular coagulation in Japan.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Morser Jdoi
10.2174/138945012799424606subject
Has Abstractpub_date
2012-03-01 00:00:00pages
421-31issue
3eissn
1389-4501issn
1873-5592pii
BSP/CDT/E-Pub/00368journal_volume
13pub_type
杂志文章,评审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::Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmeno...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990195
更新日期:2013-12-01 00:00:00
abstract::Medical chronobiology deals with the way body's rhythm influences a person's health and disease states. To match body rhythms, deliberate alteration of drug concentration is done to optimize therapeutic outcomes and minimize size effects and this approach is known as Chronotherapeutics. In general the concept of homeo...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666190527114529
更新日期:2019-01-01 00:00:00
abstract::Virtual screening for active compounds has become an essential step within the drug development pipeline. The computer based prediction of compound binding modes is one of the most time and cost efficient methods for screening ligand libraries and enrich results of potential drugs. Here we present an overview about cu...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160201105806
更新日期:2016-01-01 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::Hypertension is usually associated with deficient nitric oxide (NO) bioavailability, and therefore stimulating NO activity is an important antihypertensive strategy. Recently, many studies have shown that both nitrite and nitrate anions are not simple products of NO metabolism and indeed may be reduced back to NO. Whi...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666180816120816
更新日期:2019-01-01 00:00:00
abstract::Enzymes are proteins that act as biological catalysts to speed up cellular biochemical processes. According to their main Enzyme Commission (EC) numbers, enzymes are divided into six categories: EC-1: oxidoreductase; EC-2: transferase; EC-3: hydrolase; EC-4: lyase; EC-5: isomerase and EC-6: synthetase. Different enzym...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666181002143355
更新日期:2019-01-01 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::Androgen and androgen receptor (AR) play a critical role in the development of prostate cancer. Androgen deprivation therapy (ADT) has become the therapeutic mainstay for patients with metastatic prostate cancer. ADT can reduce the serum testosterone level from the normal range between 500 and 600 ng/dl to the castrat...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141024114736
更新日期:2014-01-01 00:00:00
abstract::Ceruloplasmin contains 95% of the copper in human serum and plays an important role in iron efflux from mammalian cells, including brain cells, due to the activity of ferroxidase, which oxidizes ferrous iron following its transfer to the cell surface via the iron transporter, ferroportin, and delivers ferric iron to e...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012802002320
更新日期:2012-08-01 00:00:00
abstract::Trauma-induced coagulopathy (TIC) is a recently described condition which traditionally has been diagnosed by the common coagulation tests (CCTs) such as prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen levels. The varying sensitivit...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160310153211
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:The intracellular multiprotein complex termed the inflammasome functions as a platform of pro-inflammatory cytokine production such as IL-1β and IL-18. Under certain conditions, however, the inflammasome produces non-canonical effects such as induction of cell death, pyroptosis and cell metabolism alteration...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160817103435
更新日期:2017-01-01 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::Pain is a complex multidimensional concept that facilitates the initiation of the signaling cascade in response to any noxious stimuli. Action potential generation in the peripheral nociceptor terminal and its transmission through various types of nociceptors corresponding to mechanical, chemical or thermal stimuli le...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666190131114244
更新日期:2019-01-01 00:00:00
abstract::Phenothiazines and structurally related compounds alongside their other biological activities are able to modulate multidrug resistance (MDR) in tumor cells. The extensive investigations on their MDR modulation effects consist part of the efforts to overcome MDR - the major obstacle in cancer chemotherapy. In this art...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006778226660
更新日期:2006-09-01 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::Diacylglycerol (DAG) kinase (DGK) modulates the balance between the two signaling lipids, DAG and phosphatidic acid (PA), by phosphorylating (consuming) DAG to yield PA. Ten mammalian DGK isozymes have been identified to date. In addition to two or three cysteine-rich C1 domains (protein kinase C-like zinc finger stru...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008785132394
更新日期:2008-08-01 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::The α7-nAChR plays critical roles in numerous organs and cells by regulating highly organ and cell typespecific functions. In this special issue different Authors have contributed to clarify the different roles played by the α7- nAChR. Post-translational processes such as receptor "underactivation" or "overactivation"...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/138945012800398946
更新日期:2012-05-01 00:00:00
abstract::It is well known that calorie restriction (CR) can retard the aging process in organisms ranging from yeast to non-human primates, and delay the onset of numerous age-related diseases including neurodegenerative disorders. Translation of the knowledge gained from CR research in animal models to disease prevention stra...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111007011281
更新日期:2010-10-01 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:BACKGROUND:The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150416115852
更新日期:2018-01-01 00:00:00
abstract::Programmed cell death, commonly associated with the term apoptosis, is an integrated intracellular program that plays a critical role in lymphoid tissue homeostasis. Alterations in this highly regulated process is a common feature of most lymphoid malignancies, thus facilitating tumor escape from traditional chemother...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010791320863
更新日期:2010-07-01 00:00:00
abstract::Our aim was to provide a narrative review regarding the prevalence, the associated pathophysiologic pathways and the potential management methods of sexual dysfunction related to ablative surgical techniques for Benign Prostatic Enlargement (BPE). Men suffering from BPE are at high risk of sexual dysfunction due to th...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200925143916
更新日期:2021-01-01 00:00:00
abstract::Natural products represent a rich resource for drug delivery and are currently being exploited to target tumour angiogenesis. A vast array of products of natural origin have been shown to have anti-angiogenic potential in preclinical models, including purified endogenous inhibitors, and exogenous compounds derived fro...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006776054951
更新日期:2006-03-01 00:00:00
abstract::Multifunctional rational drug design of protein tyrosine kinases inhibitors allows a potent drug to be utilized to treat more than one disease for greater patient benefits. Many protein tyrosine kinases (PTK), including Janus kinase 3 (JAK3) and Bruton's tyrosine kinase (BTK), have been identified as potential drug ta...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006776054997
更新日期:2006-03-01 00:00:00
abstract:BACKGROUND:Prohibitin (PHB) is overtly conserved evolutionarily and ubiquitously expressed protein with pleiotropic functions in diverse cellular compartments. However, regulation and function of these proteins in different cells, tissues and in various diseases is different as evidenced by expression of these proteins...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160824161225
更新日期:2017-11-30 00:00:00
abstract::Five programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for the treatment of locally advanced or metastatic urothelial carcinoma of the bladder and the upper urinary tract. Following the FDA and EMA restrictions of first-line treatment with Atezolizumab and Pembrolizumab in platinum...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200510015216
更新日期:2020-05-09 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::The heterogeneity of proteoglycans (PG)s contributes to their functional diversity. Many functions depend on their ability to bind and modulate the activity of components of the extracellular matrix (ECM). The ability of PGs to interact with other molecules, such as growth factors, is largely determined by the fine st...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450054863662
更新日期:2005-09-01 00:00:00