keyword
MENU ▼
Read by QxMD icon Read
search

Human carboxylesterase

keyword
https://www.readbyqxmd.com/read/29155040/radiolabelled-soman-binding-to-sera-from-rats-guinea-pigs-and-monkeys
#1
David E Lenz, Douglas Cerasoli, Donald M Maxwell
Soman is a highly toxic organophosphorus chemical warfare compound that binds rapidly and irreversibility to a variety of serine active enzymes, i.e., butyryl- and acetyl-cholinesterases and carboxylesterase. The in vivo toxicity of soman has been reported to vary significantly in different animal species, such as rats and guinea pigs or non-human primates. This species variation makes it difficult to identify appropriate animal models for therapeutic drug development under the US Food and Drug Administration (FDA) Animal Rule...
November 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29113833/the-role-of-genetic-background-in-susceptibility-to-chemical-warfare-nerve-agents-across-rodent-and-non-human-primate-models
#2
REVIEW
Liana M Matson, Hilary S McCarren, C Linn Cadieux, Douglas M Cerasoli, John H McDonough
Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies...
November 4, 2017: Toxicology
https://www.readbyqxmd.com/read/29073340/liver-targeted-small-molecule-inhibitors-of-proprotein-convertase-subtilisin-kexin-type-9-synthesis
#3
Kim Francis McClure, David W Piotrowski, Donna Petersen, Liuqing Wei, Jun Xiao, Allyn T Londregan, Adam Kamlet, Anne-Marie Dechert-Schmitt, Brian Raymer, Roger B Ruggeri, Daniel Canterbury, Chris Limberakis, Spiros Liras, Paul DaSilva-Jardine, Robert G Dullea, Paula M Loria, Benjamin Reidich, Christopher T Salatto, Heather Eng, Emi Kimoto, Karen Atkinson, Amanda King-Ahmad, Dennis Scott, Kevin Beaumont, Jeffrey R Chabot, Michael Bolt, Kevin Maresca, Kenneth Dahl, Ryosuke Arakawa, Akihiro Takano, Christer Halladin
Targeting of the human ribosome is an unprecedented therapeutic modality with a genome-wide selectivity challenge. Herein we describe a liver-targeted drug candidate that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered undruggable by small molecules. Key to the concept was the identification of pharmacologically active zwitterions designed to be retained in the liver. Oral delivery of the poorly permeable zwitterions was achieved via prodrugs susceptible to cleavage by carboxylesterase 1...
October 26, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29054529/development-of-amide-based-fluorescent-probes-for-selective-measurement-of-carboxylesterase-1-activity-in-tissue-extracts
#4
Sean D Kodani, Morgane Barthélemy, Shizuo G Kamita, Bruce Hammock, Christophe Morisseau
Carboxylesterases are well known for their role in the metabolism of xenobiotics. However, recent studies have also implicated carboxylesterases in regulating a number of physiological processes including metabolic homeostasis and macrophage development, underlying the need to quantify them individually. Unfortunately, current methods for selectively measuring the catalytic activity of individual carboxylesterases are not sufficiently sensitive to support many biological studies. In order to develop a more sensitive and selective method to measure the activity of human carboxylesterase 1 (hCE1), we generated and tested novel substrates with a fluorescent aminopyridine leaving group...
December 15, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29029320/insecticidal-mechanism-of-wintergreen-oil-against-the-health-pest-paederus-fuscipes-coleoptera-staphylinidae
#5
Zhiping Liu, Qiang Zhang, Xuan Wu, Wei Yu, Shengquan Guo
Paederus fuscipes, a health pest, causes dermatitis linearis in humans. Wintergreen oil exhibits optimal insecticidal activity against P. fuscipes. However, the insecticidal mechanism remains unclear not only in P. fuscipes but also in other pests. In this study, we explored the insecticidal mechanism of wintergreen oil in terms of its effect on the activity of acetylcholinesterase (AChE) enzyme and detoxifying enzymes (carboxylesterase, glutathione-S-transferase, and mixed function oxidase); such effect was studied by fumigation both in vivo and in vitro in P...
October 4, 2017: Journal of Medical Entomology
https://www.readbyqxmd.com/read/28985084/controlling-plasma-stability-of-hydroxamic-acids-a-medchem-toolbox
#6
Paul Hermant, Damien Bosc, Catherine Piveteau, Ronan Gealageas, BaoVy Lam, Cyril Ronco, Matthieu Roignant, Hasina Tolojanahary, Ludovic Jean, Pierre-Yves Renard, Mohamed Lemdani, Marilyne Bourotte, Adrien Herledan, Corentin Bedart, Alexandre Biela, Florence Leroux, Benoit Deprez, Rebecca Deprez-Poulain
Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability...
October 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28966098/difference-in-substrate-specificity-of-carboxylesterase-and-arylacetamide-deacetylase-between-dogs-and-humans
#7
Tomohiro Yoshida, Tatsuki Fukami, Takaya Kurokawa, Saki Gotoh, Akifumi Oda, Miki Nakajima
Carboxylesterase (CES) and arylacetamide deacetylase (AADAC) are the major enzymes responsible for the hydrolysis of various clinical drugs. Our recent study demonstrated that the identity of the responsible hydrolase can be roughly surmised based on the chemical structures of compounds in humans. Dogs are used for preclinical studies in drug development, but the substrate specificities of dog CES and AADAC remain to be clarified. The purpose of this study is to characterize their substrate specificities. We prepared recombinant dog CES1, CES2, and AADAC...
September 28, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28838926/a-comprehensive-functional-assessment-of-carboxylesterase-1-nonsynonymous-polymorphisms
#8
Xinwen Wang, Nada Rida, Jian Shi, Audrey H Wu, Barry E Bleske, Hao-Jie Zhu
Carboxylesterase 1 (CES1) is the predominant human hepatic hydrolase responsible for the metabolism of many clinically important medications. CES1 expression and activity vary markedly among individuals; and genetic variation is a major contributing factor to CES1 interindividual variability. In this study, we comprehensively examined the functions of CES1 nonsynonymous single nucleotide polymorphisms (nsSNPs) and haplotypes using transfected cell lines and individual human liver tissues. The 20 candidate variants include CES1 nsSNPs with a minor allele frequency >0...
November 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28820941/a-photoactivatable-probe-for-super-resolution-imaging-of-enzymatic-activity-in-live-cells
#9
Elias A Halabi, Zacharias Thiel, Nils Trapp, Dorothea Pinotsi, Pablo Rivera-Fuentes
A dual-activatable, fluorogenic probe was developed to sense esterase activity with single-molecule resolution. Without enzymatic pre-activation, the diazoindanone-based probe has an electron-poor core and, upon irradiation, undergoes Wolff rearrangement to give a ring-expanded xanthene core that is nonemissive. If the probe is pre-activated by carboxylesterases, the tricyclic core becomes electron-rich, and the photoinduced Wolff rearrangement produces a highly emissive rhodol dye. Live-cell and solution studies confirmed the selectivity of the probe and revealed that the photoactivated dye does not diffuse away from the original location of activation because the intermediate ketene forms a covalent bond with surrounding macromolecules...
September 5, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28782481/rational-approaches-design-strategies-structure-activity-relationship-and-mechanistic-insights-for-esterase-inhibitors
#10
Harbinder Singh, Jatinder Vir Singh, Navdeep Kaur, Mohit Sanduja, Gurpreet Singh, Preet Mohinder Singh Bedi, Sahil Sharma
BACKGROUND: Esterase is an enzyme that splits esters into an acid and alcohol. Varieties of esterases are present in human body to control diverse set of cellular processes and execute their specific functions. It can be seen that any increase in metabolites produced by these enzymes lead to severe pathological conditions like Alzheimer disease, hypercholesterolemia etc. OBJECTIVE: Numerous esterase inhibitors have been developed and reported by the researchers around the globe, but not systematically summarized yet...
August 7, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28760607/phenolic-glycosides-and-monoterpenoids-from-the-roots-of-euphorbia-ebracteolata-and-their-bioactivities
#11
An-Hua Wang, Xiao-Kui Huo, Lei Feng, Cheng-Peng Sun, Sa Deng, Hou-Li Zhang, Bao-Jing Zhang, Xiao-Chi Ma, Jing-Ming Jia, Chao Wang
The bioactive substance investigation of Euphorbia ebracteolata obtained 17 compounds by various chromatographic techniques. Their structures were elucidated using widely spectroscopic data, including ESI-MS, HRESI-MS, CD, 1D- and 2D-NMR, which gave 5 new phenolic glucosides and 4 new monoterpenoids. The phenolic glucosides and monoterpenoids showed the inhibitory effect against the human carboxylesterase-2 (hCE-2) using a fluorescence bioassay in vitro, with the strongest inhibitor compound 4 (IC50 7.17μM)...
September 2017: Fitoterapia
https://www.readbyqxmd.com/read/28737453/the-metabolism-and-drug-drug-interaction-potential-of-the-selective-prostacyclin-receptor-agonist-selexipag
#12
Carmela Gnerre, Jérôme Segrestaa, Swen Seeland, Päivi Äänismaa, Thomas Pfeifer, Stephane Delahaye, Ruben de Kanter, Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber
- The metabolism of selexipag has been studied in vivo in man and the main excreted metabolites were identified. Also, metabolites circulating in human plasma have been structurally identified and quantified. - The main metabolic pathway of selexipag in man is the formation of the active metabolite ACT-333679. Other metabolic pathways include oxidation and dealkylation reactions. All primary metabolites undergo subsequent hydrolysis of the sulphonamide moiety to their corresponding acids. ACT-333679 undergoes conjugation with glucuronic acid and aromatic hydroxylation to P10, the main metabolite detected in human faeces...
July 24, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28713276/structure-activity-relationships-of-pentacyclic-triterpenoids-as-potent-and-selective-inhibitors-against-human-carboxylesterase-1
#13
Li-Wei Zou, Tong-Yi Dou, Ping Wang, Wei Lei, Zi-Miao Weng, Jie Hou, Dan-Dan Wang, Yi-Ming Fan, Wei-Dong Zhang, Guang-Bo Ge, Ling Yang
Human carboxylesterase 1 (hCE1), one of the most important serine hydrolases distributed in liver and adipocytes, plays key roles in endobiotic homeostasis and xenobiotic metabolism. This study aimed to find potent and selective inhibitors against hCE1 from phytochemicals and their derivatives. To this end, a series of natural triterpenoids were collected and their inhibitory effects against human carboxylesterases (hCEs) were assayed using D-Luciferin methyl ester (DME) and 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB) as specific optical substrate for hCE1, and hCE2, respectively...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28677105/carboxylesterases-in-lipid-metabolism-from-mouse-to-human
#14
REVIEW
Jihong Lian, Randal Nelson, Richard Lehner
Mammalian carboxylesterases hydrolyze a wide range of xenobiotic and endogenous compounds, including lipid esters. Physiological functions of carboxylesterases in lipid metabolism and energy homeostasis in vivo have been demonstrated by genetic manipulations and chemical inhibition in mice, and in vitro through (over)expression, knockdown of expression, and chemical inhibition in a variety of cells. Recent research advances have revealed the relevance of carboxylesterases to metabolic diseases such as obesity and fatty liver disease, suggesting these enzymes might be potential targets for treatment of metabolic disorders...
July 4, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28667306/crystal-structure-of-pelagibacterium-halotolerans-pe8-new-insight-into-its-substrate-binding-pattern
#15
Ying-Yi Huo, Suhua Li, Jing Huang, Zhen Rong, Zhao Wang, Zhengyang Li, Rui Ji, Siyun Kuang, Heng-Lin Cui, Jixi Li, Xue-Wei Xu
Lysophospholipase_carboxylesterase (LPCE) has highly conserved homologs in many diverse species ranging from bacteria to humans, as well as substantial biological significance and potential therapeutic implications. However, its biological function and catalytic mechanism remain minimally investigated because of the lack of structural information. Here, we report the crystal structure of a bacterial esterase PE8 belonging to the LPCE family. The crystal structure of PE8 was solved with a high resolution of 1...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28647665/comparative-metabolism-of-ddao-benzoate-in-liver-microsomes-from-various-species
#16
Hong-Ying Ma, Jia-Da Yang, Jie Hou, Li-Wei Zou, Qiang Jin, Da-Cheng Hao, Jing Ning, Guang-Bo Ge, Ling Yang
DDAB (6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate) is a newly developed near-infrared fluorescent probe for human carboxylesterase 2 (hCE2), exhibiting high specificity and good reactivity for real-time monitoring the enzymatic activities of hCE2 in complex biological systems. In order to explore the applicability of DDAB in commonly used animal species, the interspecies difference in DDAB hydrolysis was carefully investigated by using liver microsomes from human and five experimental animals including mouse, rat, dog, minipig and monkey...
October 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28619281/metabolism-of-ko143-an-abcg2-inhibitor
#17
Ke Liu, Junjie Zhu, Yixian Huang, Chaoyue Li, Jie Lu, Madhav Sachar, Song Li, Xiaochao Ma
The ATP-binding cassette sub-family G member 2 (ABCG2) plays an important role in modulating drug disposition and endobiotic homeostasis. KO143 is a potent and relatively selective ABCG2 inhibitor. We found that the metabolic stability of KO143 was very poor in human liver microsomes (HLM). Our further studies illustrated that the tert-butyl ester group in KO143 can be rapidly hydrolyzed and removed by carboxylesterase 1. This metabolic pathway was confirmed as a major pathway of KO143 metabolism in both HLM and mice...
March 6, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28536421/assessment-of-tissue-specific-accumulation-elimination-and-toxic-effects-of-dichlorodiphenyltrichloroethanes-ddts-in-carp-through-aquatic-food-web
#18
Shanshan Di, Ruiquan Liu, Zhongnan Tian, Cheng Cheng, Li Chen, Wenjun Zhang, Zhiqiang Zhou, Jinling Diao
Microcosms containing DDT spiked-sediment, Tubifex tubifex and carp (Cyprinus carpio) were constructed to simulate a freshwater system. The accumulation, elimination and toxic effects of DDT (p,p'-DDT, o,p'-DDT), and its metabolites DDD (p,p'-DDD, o,p'-DDD) and DDE (p,p'-DDE, o,p'-DDE) were studied in T. tubifex and carp. Tissue/organ distributions of DDTs were also investigated in carp. The bioaccumulation and elimination of DDT differed in T. tubifex, carp and its tissues/organs. Unimodal or bimodal distributions were observed, and the concentrations of DDT metabolites (DDD and p,p'-DDE) increased over time...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28532270/predominant-contributions-of-carboxylesterase-1-and-2-in-hydrolysis-of-anordrin-in-humans
#19
Jinfang Jiang, Xiaoyan Chen, Dafang Zhong
1. Anordrin (2α, 17α-diethynyl-A-nor-5α-androstane-2β, 17β-diol diproprionate) is post-coital contraceptive drug that is on the market in China for more than 30 years. This study aims to elucidate enzymes involved in anordrin hydrolysis, and to evaluate the significant role of carboxylesterases in anordrin hydrolysis in humans. 2. Human liver and intestinal microsomes, recombinant human carboxylesterase were selected as enzyme sources. In human liver microsomes, intrinsic clearance was 684 ± 83 μL/min/mg protein, which was considerably higher than the value of intestine microsomes (94...
June 7, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28473993/salvia-miltiorrhiza-roots-against-cardiovascular-disease-consideration-of-herb-drug-interactions
#20
REVIEW
Feng Chen, Li Li, Dan-Dan Tian
Salvia miltiorrhiza root (Danshen) is widely used in Asia for its cardiovascular benefits and contains both hydrophilic phenolic acids and lipophilic tanshinones, which are believed to be responsible for its therapeutic efficacy. This review summarized the effects of these bioactive components from S. miltiorrhiza roots on pharmacokinetics of comedicated drugs with mechanic insights regarding alterations of protein binding, enzyme activity, and transporter activity based on the published data stemming from both in vitro and in vivo human studies...
2017: BioMed Research International
keyword
keyword
120988
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"