Abstract：
:The selenoprotein thioredoxin reductase (TXNRD) is a promising therapeutic target for cancer. To discover novel TXNRD inhibitors, a library of α, β-unsaturated carbonyl compounds were applied in structure-based virtual screening for the selection of hit compounds. Fifteen top-ranked compounds were further validated experimentally, exhibiting potent inhibition of TXNRD and remarkable cytotoxicity to cancer cells. The further binding mode analysis indicated that multiple noncovalent interactions between the inhibitors and the active pocket of TXNRD facilitated the formation of covalent bonds between the Sec498 on TXNRD and the α, β-unsaturated carbonyl groups on inhibitors. Results from both simulations and experiments demonstrated that Sec498 is the prime interaction site for the inhibition of TXNRD. Taking compound 7 as an example, the inhibition of TXNRD by compounds promoted oxidative stress-mediated apoptosis of cancer cells. Given these findings, novel TXNRD inhibitors may be discovered and introduced to the growing fields of small molecule drugs against TXNRD.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Liu R,Shi D,Zhang J,Li X,Han X,Yao X,Fang Jdoi
10.1016/j.taap.2019.03.014subject
Has Abstractpub_date
2019-05-01 00:00:00pages
106-116eissn
0041-008Xissn
1096-0333pii
S0041-008X(19)30104-8journal_volume
370pub_type
杂志文章abstract：:The 2009 Toxicology and Risk Assessment Conference (TRAC) session on "Advances in Exposure and Toxicity Assessment of Particulate Matter" was held in April 2009 in West Chester, OH. The goal of this session was to bring together toxicology, geology and risk assessment experts from the Department of Defense and academi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2010.10.020
更新日期：2011-07-15 00:00:00
abstract：:A number of methods have been developed to assess the impact of a xenobiotic on the various components of the immune system. For risk analysis, it is necessary to determine what degree of chemically induced immune perturbation translates into altered host resistance. Natural killer (NK) cells play a pivotal role in th...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2001.9298
更新日期：2001-12-15 00:00:00
abstract：:The issue of Elongated Mineral Particles (EMP) in building materials has been revealed during roadworks in 2013 in France. In fact, road coating aggregates are made of specific rock gravels that can contain Naturally Occurring Asbestos (NOA), which is mainly actinolite. The legislation refers to six regulatory asbesto...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.04.027
更新日期：2018-12-15 00:00:00
abstract：INTRODUCTION:Noncirrhotic portal fibrosis has been reported to occur in humans due to prolonged intake of arsenic contaminated water. Further, oxystress and hepatic fibrosis have been demonstrated by us in chronic arsenic induced hepatic damage in murine model. Cytokines like tumor necrosis factor alpha (TNF-alpha) and...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2004.08.010
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abstract：:MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for ki...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2016.01.018
更新日期：2016-12-01 00:00:00
abstract：:Radiolabeled 1-naphthyl-beta-D-glucuronide and 1-naphthyl-beta-D-glucoside were synthesized from 1-[14C]naphthol. The fate of the three compounds in male mice was studied. After a po dose of 45 mg/kg of 1-naphthol, 100 mg/kg of 1-naphthyl glucuronide, and 100 mg/kg of 1-naphthyl glucoside, 95, 93, and 81%, respectivel...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90313-7
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abstract：:The vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of alpha-tocopheryl maleamide (alpha-TAM), an esterase-resistant analogue of alpha-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of al...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.01.027
更新日期：2009-06-15 00:00:00
abstract：:Lung toxicity induced by sulfur mustard is associated with inflammation and oxidative stress. To elucidate mechanisms mediating pulmonary damage, we used 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. Male mice (B6129) were treated intratracheally with CEES (3 or 6 mg/kg) or control. Animals were...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2010.10.027
更新日期：2011-02-01 00:00:00
abstract：:3-Methylindole (3MI), a fermentation product of tryptophan produced by intestinal and ruminal microflora, has been shown to cause pneumotoxicity in several species subsequent to cytochrome P450-mediated biotransformation. Among several species studied, rabbits are comparatively resistant to 3MI-induced pneumotoxicity,...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1186
更新日期：1993-10-01 00:00:00
abstract：:Diurnal patterns of eating, drinking, locomotor activity, and rearing in male Fischer-344 rats were examined for 11 days after a single oral dose of triethyltin bromide (TET) at 0, 1.5, 3, or 5 mg/kg. The 5 mg/kg group exhibited a time-related drop in food consumption and body weight until 3 of 10 rats were sacrificed...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90342-x
更新日期：1986-09-30 00:00:00
abstract：:Benzene is used at large volumes in many different human activities. Hematotoxicity and cancer-causation as a result of benzene exposure was recognized many years ago, but the mechanisms involved remain unclear. Aberrant regulation of gap junction intercellular communication (GJIC) has been linked to both cancer induc...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.07.022
更新日期：2008-11-01 00:00:00
abstract：:4-Alkylbicyclophosphates, R1C(CH2O)3P(O), with suitable R1 substituents (e.g., t-butyl, isopropyl, or cyclohexyl) are highly toxic compounds [mouse intraperitoneal (ip) LD50 values 0.036-0.52 mg/kg] and are potent noncompetitive gamma-aminobutyric acid (GABA) antagonists. 4-Alkylmonocyclophosphates of the type R1(HOCH...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(85)90119-x
更新日期：1985-10-01 00:00:00
abstract：:Daily subcutaneous administration of 20 or 100 mg/kg gentamicin for 4 days significantly decreased pyridoxal-5'-phosphate and lysosomal specific phosphatidylinositol-phospholipase C (PI-PLC) in newborn rat kidney. The fall in PI-PLC was associated with an elevation in renal phosphatidylinositol, phosphatidylserine, an...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90111-7
更新日期：1989-06-01 00:00:00
abstract：:The aims of this study were to investigate whether several histamine receptor agonists and antagonists are subjected to receptor-independent ion trapping into acidic organelles, and whether this sequestration influences their pharmacological or toxicological properties. Vacuolar (V)-ATPase-dependent intracellular sequ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.01.028
更新日期：2008-06-15 00:00:00
abstract：:Technologies that generate information about the genome are being used to explore changes in gene expression and related proteins following exposure to chemicals. Conceptually, this information allows a greater understanding of genomic level mRNA expression (transcriptomics), cell and tissue protein expression (proteo...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2005.01.044
更新日期：2005-09-01 00:00:00
abstract：:Chelating agents commonly used in therapy of heavy metal intoxication alter the levels of essential metals in liver, kidneys, and serum. Induction of metallothionein synthesis in liver occurs following exposure to a variety of chemical and environmental insults and, in some cases, has been attributed to enhanced hepat...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(85)90391-6
更新日期：1985-09-30 00:00:00
abstract：:Lipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in the initiation of many pharmacological agent-induced signaling pathways and toxicological effects. The structure of lipid rafts is dynamic, resulting in an ever-changing content of both lipids a...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2012.01.007
更新日期：2012-03-15 00:00:00
abstract：:Assessment of toxic or mutagenic risks associated with phosphorothioate oligonucleotides (PTO) is important. In vitro and in vivo data have shown that PTOs are nontoxic and nonmutagenic. However, these studies do not address interactions between PTOs and other compounds. The sulfur on PTOs may provide a novel reactive...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1995.1126
更新日期：1995-07-01 00:00:00
abstract：:WHO has highlighted the need to evaluate dermal toxicity of mycotoxins including Patulin (PAT), detected in several fruits. In this study the skin carcinogenic potential of topically applied PAT was investigated. Single topical application of PAT (400 nmol) showed enhanced cell proliferation (~2 fold), along with incr...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.09.012
更新日期：2011-12-01 00:00:00
abstract：:Gastric cancer ranks as the third leading cause of cancer-related death worldwide. The uncontrolled tumor growth and robust metastasis are key factors to cause the cancer patient death. Mechanistically, aberrant activation of Notch and NF-κB signaling pathways plays pivotal roles in the initiation and metastasis of ga...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2019.114870
更新日期：2020-02-01 00:00:00
abstract：:We expressed rat Na(v)1.6 sodium channels in combination with the rat beta(1) and beta(2) auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2010.07.001
更新日期：2010-09-15 00:00:00
abstract：:This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the current model were comp...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.03.005
更新日期：2012-05-01 00:00:00
abstract：:Vinylcyclohexene (VCH) is an industrial byproduct that is known to cause the destruction of ovarian follicles in mice. Its analog, 4-phenylcyclohexene (4PC), is a volatile product from latex-backed carpeting. These studies were undertaken to assess the structure-activity relationships of these compounds and the potent...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1073
更新日期：1993-04-01 00:00:00
abstract：:It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/an...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2013.05.016
更新日期：2013-10-01 00:00:00
abstract：:Male reproductive health has received considerable attention in recent years. In addition to declining sperm quality, fertility problems and increased incidence of testicular cancer, there is accumulating evidence that genetic damage, in the form of unrepaired DNA lesions or de novo mutations, may be transmitted via s...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2005.01.060
更新日期：2005-09-01 00:00:00
abstract：:Juglone (5-hydroxy-1,4-naphtoquinone) is a natural toxin produced by walnut trees. In this study we show that juglone differentially reduces viability of human cells in culture. Normal fibroblast were found to be especially sensitive to juglone and lost viability primarily through a rapid apoptotic and necrotic respon...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.03.005
更新日期：2005-11-15 00:00:00
abstract：:Carbon tetrachloride (CCl4) has been studied extensively for its hepatotoxic effects. There is a paucity of information, however, about its tissue deposition following administration by different routes and patterns of exposure. The specific objective of this study was to delineate the uptake, distribution, and elimin...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.8079
更新日期：1997-03-01 00:00:00
abstract：:The putative neurotoxicity of the organophosphorus compound triphenyl phosphite (TPP) was examined in Long Evans, adult male rats. Animals were exposed to two 1.0 ml/kg (1184 mg/kg) injections (sc) of TPP spaced 1 week apart and sampled for biochemical and neuropathological examination. At the time of sampling, rats d...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90297-8
更新日期：1986-04-01 00:00:00
abstract：:Methemoglobin formation, as well as hemoglobin or DNA adducts, are useful biomarkers of occupational exposure to certain arylamines. It has been suggested that, in liver from animals not treated with a cytochrome P450 (CYP) inducer, hepatic CYP1A2 is the major P450 involved in N-hydroxylation. This is the first step i...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2002.9398
更新日期：2002-05-15 00:00:00
abstract：:The disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran (TCDF) was investigated in rainbow trout (Oncorhynchus mykiss) in order to better understand the metabolic and physiological factors that modulate the fate of this extremely toxic compound in rainbow trout compared to other species. The fish were dosed ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0183
更新日期：1996-08-01 00:00:00
