Abstract:
:Antibodies that block cytokine function provide a powerful therapeutic tool especially for the treatment of autoimmune diseases. Cytokines are a group of small hydrophilic glycoproteins that bind their receptors on the cell surface and subsequently activate intracellular signalling cascades, such as the JAK/STAT pathway. A bulk of evidence has demonstrated that genetic mutations in signalling molecules can cause immunodeficiencies and malignant cell growth. As a result, several drug companies have begun to develop therapeutics that inhibit the function of JAK tyrosine kinases. Currently, two JAK inhibitors, tofacitinib and ruxolitinib, are used in the clinic for treating rheumatoid arthritis and myeloproliferative diseases, respectively. Inhibiting JAK function has been shown to efficiently prevent the uncontrolled growth of cancerous cells and to harness overly active immune cells. In the future, other small molecule compounds are likely to come into clinical use, and intense work is ongoing to develop inhibitors that specifically target the constitutively active mutant JAKs. This MiniReview will summarize the basic features of the JAK/STAT pathway, its role in human disease and the therapeutic potential of JAK/STAT inhibitors.
journal_name
Basic Clin Pharmacol Toxicoljournal_title
Basic & clinical pharmacology & toxicologyauthors
Aittomäki S,Pesu Mdoi
10.1111/bcpt.12164subject
Has Abstractpub_date
2014-01-01 00:00:00pages
18-23issue
1eissn
1742-7835issn
1742-7843journal_volume
114pub_type
杂志文章,评审abstract::Certain chemotherapeutic agents subject cells to oxidative stress, thereby promoting adverse effects. However, the molecular machinery governing 5-fluorouracil (5-FU)-mediated myelotoxicity is obscure. The purpose of this study was to clarify whether 5-FU-induced myelotoxicity is a cause of oxidative stress. Treatment...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2010.00621.x
更新日期:2011-01-01 00:00:00
abstract::Interest in proteomics as a tool for drug development and a myriad of other applications continues to expand at a rapid rate. Proteomic analyses have recently been conducted on tissues, biofluids, subcellular components and enzymatic pathways as well as various disease and toxicological states, in both animal models a...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
doi:10.1111/j.1742-7843.2006.pto_391.x
更新日期:2006-05-01 00:00:00
abstract::This study was designed to investigate the therapeutic effect of sodium formononetin-3'-sulphonate (Sul-F), a water-soluble derivate of formononetin, on acute myocardial infarction in rats. The results showed that treatment with Sul-F significantly prevented the elevation of ST-segment level, decreased the contents of...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2011.00676.x
更新日期:2011-06-01 00:00:00
abstract::QF-036 is an HIV-1 maturation inhibitor in pre-clinical development, and its antiviral activity against a laboratory HIV-1 strain and two drug-resistant strains was determined in the C8166 line. QF-036 was also subjected to absorption, distribution and metabolism (ADM) assessment in vitro, and pharmacokinetic profiles...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.13504
更新日期:2021-02-01 00:00:00
abstract::The specific protein target of delta9-tetrahydrocannabinol (delta9-THC), the main active ingredient of Cannabis sativa L., was characterized from rat brain nearly 20 years ago, and several endogenous compounds and proteins comprising the endocannabinoid (eCB) system have since been discovered. It has become evident th...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
doi:10.1111/j.1742-7843.2007.00130.x
更新日期:2007-11-01 00:00:00
abstract::Several studies in the Northeastern region of Brazil have demonstrated an association between hypertension in adult populations and prenatal and postnatal undernutrition. The central hypothesis we proposed was that hypertension could be favoured by programmed alterations in branches of the renal arachidonic pathway an...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2010.00625.x
更新日期:2011-02-01 00:00:00
abstract::Three diterpenoid quinones (royleanone- SAR 3, horminone- SAR 26, and acetyl horminone- SAR 43) isolated from the roots of Salvia officinalis L. were tested for their cytotoxic and DNA-damaging activity in human colon carcinoma cells Caco-2 and human hepatoma cells HepG2 cultured in vitro. Cytotoxicity was measured by...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2004.pto940605.x
更新日期:2004-06-01 00:00:00
abstract::Natural dietary antioxidants are extensively studied for their ability to protect cells from miscellaneous damages. Origanum majorana L., Lamiaceae, is a potent antioxidant. The effect of administration of O. majorana (volatile oil, alcoholic and aqueous extracts) on oral administration of lead acetate in the diet of ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2005.pto_136.x
更新日期:2005-10-01 00:00:00
abstract::Since the introduction of antivenom administration over a century ago to treat venomous snake bite, it has been the most effective therapy for saving life and limb. However, this treatment is not always effective and not without potential life-threatening side effects. We tested a new paradigm to abrogate the plasmati...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12654
更新日期:2017-02-01 00:00:00
abstract::Prolyl oligopeptidase (POP) has been connected to learning, memory and mood. Changes in serum or plasma POP activity have been linked to psychiatric disorders. POP has been thought to interfere in these conditions by cleaving neuroactive peptides or via the phosphatidylinositol second messenger system. However, little...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2010.00626.x
更新日期:2011-01-01 00:00:00
abstract::The era of immunotherapies was unleashed in 2010 with the Food and Drug Administration (FDA) approval of the first therapeutic vaccine sipuleucel-T as a standard treatment for metastatic prostate cancer. Next, the first immune-activating anticytotoxic lymphocyte antigen-4 (CTLA-4) antibody ipilimumab exhibiting 'immun...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
doi:10.1111/bcpt.12320
更新日期:2015-01-01 00:00:00
abstract::Cytochrome P450 3A4 (CYP3A4) is quantitatively the most important P450 enzyme in adults. It is suggested that CYP3A4 genetic polymorphisms may influence the rate of the metabolism and elimination of CYP3A4 substrates in human beings. Ibrutinib is an anticancer drug and primarily metabolized by CYP3A4. The aim of this ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12934
更新日期:2018-04-01 00:00:00
abstract::We evaluated the effects of conjugated enzyme-nerve agent product resulting from the inhibition of bioscavenger human serum butyrylcholinesterase (Hu BChE) by nerve agents soman or VX. Rats were trained on a multiple Fixed-Ratio 32, Extinction 30 sec. (FR32, Ext30) schedule of food reinforcement and then injected (i.m...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2009.00508.x
更新日期:2010-05-01 00:00:00
abstract::While the physiological function and mechanisms of agonist-dependent G protein-coupled receptor (GPCR) internalization have been extensively studied, the functional characterization of constitutive internalization of these critically important receptors has received less attention. Here we relate the constitutive inte...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.13274
更新日期:2020-06-01 00:00:00
abstract::The currently recommended first-line treatments of erectile dysfunction (ED), phosphodiesterase type 5 inhibitors (PDE5i), for example sildenafil, are efficacious in many patients with ED of vascular origin, but this therapy is insufficient in approximately 30-40% of men with ED where there is also a neuronal affectio...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
doi:10.1111/bcpt.12653
更新日期:2016-10-01 00:00:00
abstract::Evidence of poor prescribing is widespread including overuse of medicines, underuse of effective medicines, avoidable adverse drug reactions and medication errors. Junior doctors who have recently graduated are responsible for much of the prescribing that takes place in hospitals and are implicated in many of the adve...
journal_title:Basic & clinical pharmacology & toxicology
pub_type:
doi:10.1111/j.1742-7843.2007.00141.x
更新日期:2007-12-01 00:00:00
abstract::This study investigated the antinociceptive effects of zerumbone in chemical behavioural models of nociception in mice. Zerumbone given through intraperitoneal route (i.p.) produced dose-related antinociception when assessed on acetic acid-induced abdominal writhing test in mice. In addition, the i.p. administration o...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2010.00635.x
更新日期:2011-03-01 00:00:00
abstract::Nicotine-methadone interactions have been studied in human beings and in various experimental settings regarding addiction, reward and pain. Most methadone maintenance treatment patients are smokers, and methadone administration has been shown to increase cigarette smoking. Previous in vitro studies have shown that me...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12317
更新日期:2015-04-01 00:00:00
abstract::Newly developed acetylcholinesterase reactivators K117 [1,5-bis(4-hydroxyiminomethylpyridinium)-3-oxapentane dichloride] and K127 [(1-(4-hydroxyiminomethylpyridinium)-5-(4-carbamoylpyridinium)-3-oxapentane dibromide)] were tested for their potency to reactivate tabun-inhibited human brain cholinesterases. Pralidoxime ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2009.00421.x
更新日期:2009-09-01 00:00:00
abstract::The present study was carried out to evaluate the ameliorative effects of kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days signific...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2007.00005.x
更新日期:2007-01-01 00:00:00
abstract::In this study, we tested the hypothesis that fasudil, a Rho kinase inhibitor, would protect against contrast-induced acute kidney injury (CI-AKI) in a mouse model and attempted to elucidate the mechanism involved. Mice subjected to unilateral ligation of the left anterior renal pedicle were divided into four groups: (...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12895
更新日期:2018-02-01 00:00:00
abstract::Levels of cyclooxygenase-2 (COX-2) mRNA, but not those of COX-1, were reported to be raised significantly after peripheral inflammation in the rat spinal cord. The aim of the present study was to ascertain whether this pattern of COX-2 and COX-1 expression applies also to other pain conditions induced by surgical proc...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2006.pto_457.x
更新日期:2006-08-01 00:00:00
abstract::Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12722
更新日期:2017-04-01 00:00:00
abstract::Although commonly associated with obesity, non-alcoholic fatty liver disease (NAFLD) is also present in the lean population representing a unique disease phenotype. Affecting 25% of the world's population, NAFLD is associated with increased mortality especially when progressed to non-alcoholic steatohepatitis (NASH). ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.13082
更新日期:2018-12-01 00:00:00
abstract::One of the most common risks after a heart transplant is bleeding. In this study, the effect of desmopressin administration on the amount of bleeding and transfusion requirements after heart transplant surgery was investigated. In a double-blind clinical trial, 48 patients who were candidates for heart transplant surg...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcpt.12780
更新日期:2017-09-01 00:00:00
abstract::The cannabinoid 1 receptor antagonist AM 251 is known to block the inhibitory effects of endocannabinoids and synthetic cannabinoid agonists on transmitter release through an action at presynaptic cannabinoid 1 receptors in brain. We examined the ability of AM 251 to inhibit sodium channel-dependent functions and the ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2004.pto940204.x
更新日期:2004-02-01 00:00:00
abstract::DOV 216,303, an inhibitor of serotonin, noradrenaline and dopamine reuptake, belongs to a new line of drugs called 'triple reuptake inhibitors' that have been proposed for treatment of depression. The addictive drug cocaine has similar mechanism of action and exerts rewarding effects by blocking reuptake of dopamine, ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12182
更新日期:2014-06-01 00:00:00
abstract::In cardiovascular and metabolic diseases, small resistance arteries may show the presence of structural alterations. In particular, in essential hypertension, an increased media-to-lumen ratio of subcutaneous small arteries with no change in the total amount of vascular wall tissue (eutrophic remodelling) has already ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
doi:10.1111/j.1742-7843.2011.00786.x
更新日期:2012-01-01 00:00:00
abstract::The post-injection olanzapine delirium/sedation syndrome (PDSS) was observed in a 60-year-old Caucasian, schizophrenic, non-smoker and underweight [body mass index (BMI), 18.2 kg/m(2) ] women after the fourth intramuscular injection of 405 mg olanzapine pamoate. Clinical symptoms of PDSS were similar to those of acute...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12394
更新日期:2015-09-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) and MSC-derived small extracellular vesicles (sEVs) are promising candidates for cell-based and cell-free regenerative medicine, respectively. By virtue of their multiple lineage differentiation capacity, MSCs have been implicated as an ideal tool for bone and cartilage regeneration. Howe...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.13478
更新日期:2021-01-01 00:00:00