ELIZA

return kwic search for showed out of >500 occurrences
663834 occurrences (No.9 in the rank) during 5 years in the PubMed. [cache]

383) AADAC variants with R248S or X400Q showed lower activity than wild type (5% or 21%, respectively), whereas those with V172I showed higher activity than wild type (174%).

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PMID:33446525 DOI:10.1124/dmd.120.000295

2021 Drug metabolism and disposition: the biological fate of chemicals

* Role of Human Arylacetamide Deacetylase (AADAC) on Hydrolysis of Eslicarbazepine Acetate and Effects of AADAC Genetic Polymorphisms on Hydrolase Activity.

- Human arylacetamide deacetylase (AADAC) plays a role in the detoxification or activation of drugs and is sometimes involved in the incidence of toxicity by catalyzing hydrolysis reactions. AADAC prefers compounds with relatively small acyl groups, such as acetyl groups. Eslicarbazepine acetate, an antiepileptic drug, is a prodrug rapidly hydrolyzed to eslicarbazepine. We sought to clarify whether AADAC might be responsible for the hydrolysis of eslicarbazepine acetate. Eslicarbazepine acetate was efficiently hydrolyzed by human intestinal and liver microsomes and recombinant human AADAC. The hydrolase activities in human intestinal and liver microsomes were inhibited by epigallocatechin gallate, a specific inhibitor of AADAC, by 82% and 88% of the control, respectively. The hydrolase activities in liver microsomes from 25 human livers were significantly correlated (r = 0.87, P < 0.001) with AADAC protein levels, suggesting that the enzyme AADAC is responsible for the hydrolysis of eslicarbazepine acetate. The effects of genetic polymorphisms of AADAC on eslicarbazepine acetate hydrolysis were examined by using the constructed recombinant AADAC variants with T74A, V172I, R248S, V281I, N366K, or X400Q. AADAC variants with R248S or X400Q showed lower activity than wild type (5% or 21%, respectively), whereas those with V172I showed higher activity than wild type (174%). Similar tendencies were observed in the other four substrates of AADAC; that is, p-nitrophenyl acetate, ketoconazole, phenacetin, and rifampicin. Collectively, we found that eslicarbazepine acetate is specifically and efficiently hydrolyzed by human AADAC, and several AADAC polymorphic alleles would be a factor affecting the enzyme activity and drug response. SIGNIFICANCE STATEMENT: This is the first study to clarify that arylacetamide deacetylase (AADAC) is responsible for the activation of eslicarbazepine acetate, an antiepileptic prodrug, to eslicarbazepine, an active form, in the human liver and intestines. In addition, we found that several AADAC polymorphic alleles would be a factor affecting the enzyme activity and drug response.

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[frequency of next (right) word to showed]

(1)197 that	(10)5 higher	(19)3 moderate	(28)2 large
(2)50 a	(11)5 significantly	(20)3 more	(29)2 lower
(3)23 the	(12)4 differential	(21)3 mostly	(30)2 reduced
(4)14 no	(13)4 greater	(22)3 promising	(31)2 remarkable
(5)12 an	(14)4 positive	(23)2 clinically	(32)2 similar
(6)11 significant	(15)3 better	(24)2 efficacy	(33)2 stereoselectivity
(7)6 good	(16)3 extensive	(25)2 hypersensitivity	(34)2 strong
(8)6 high	(17)3 how	(26)2 impairments
(9)5 elevated	(18)3 low	(27)2 increased

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--- WordNet output for showed --- Overview of verb show The verb show has 12 senses (first 11 from tagged texts) 1. (136) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (63) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (57) testify, bear witness, prove, evidence, show -- (provide evidence for; "The blood test showed that he was the father"; "Her behavior testified to her incompetence") 4. (43) show -- (make visible or noticeable; "She showed her talent for cooking"; "Show me your etchings, please") 5. (32) picture, depict, render, show -- (show in, or as in, a picture; "This scene depicts country life"; "the face of the child is rendered with much tenderness in this painting") 6. (24) express, show, evince -- (give expression to; "She showed her disappointment") 7. (24) indicate, point, designate, show -- (indicate a place, direction, person, or thing; either spatially or figuratively; "I showed the customer the glove section"; "He pointed to the empty parking space"; "he indicated his opponents") 8. (11) show, show up -- (be or become visible or noticeable; "His good upbringing really shows"; "The dirty side will show") 9. (7) read, register, show, record -- (indicate a certain reading; of gauges and instruments; "The thermometer showed thirteen degrees below zero"; "The gauge read `empty'") 10. (6) show -- (give evidence of, as of records; "The diary shows his distress that evening") 11. (2) usher, show -- (take (someone) to their seats, as in theaters or auditoriums; "The usher showed us to our seats") 12. show -- (finish third or better in a horse or dog race; "he bet $2 on number six to show") --- WordNet end ---