PERFORM Publications

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Title		Authors	PubMed ID
1	Cross-species evaluation of TANGO2 homologs, including HRG-9 and HRG-10 in em Caenorhabditis elegans, /em challenges a proposed role in heme trafficking	Sandkuhler SE; Youngs KS; Gottipalli O; Owlett LD; Bandora MB; Naaz A; Kim E; Wang L; Wojtovich A; Gupta V; Sacher M; Mackenzie SJ;	41504601 BIOLOGY
2	Global survey of secondary metabolism in em Aspergillus niger /em via activation of specific transcription factors	Semper C; Pham TTM; Ram S; Palys S; Evdokias G; Ouedraogo JP; Moisan MC; Geoffrion N; Reid I; Di Falco M; Bailey Z; Tsang A; Benoit-Gelber I; Savchenko A;	40852424 GENOMICS
3	Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans	Costa DN; Santosa S; Jensen MD;	39869194 SOH
4	Lactate's behavioral switch in the brain: An in-silico model	Soltanzadeh M; Blanchard S; Soucy JP; Benali H;	37865309 PERFORM
5	The Adr1 transcription factor directs regulation of the ergosterol pathway and azole resistance in Candida albicans	Shrivastava M; Kouyoumdjian GS; Kirbizakis E; Ruiz D; Henry M; Vincent AT; Sellam A; Whiteway M;	37791798 BIOLOGY
6	The Sugar Metabolic Model of Aspergillus niger Can Only Be Reliably Transferred to Fungi of Its Phylum	Li J; Chroumpi T; Garrigues S; Kun RS; Meng J; Salazar-Cerezo S; Aguilar-Pontes MV; Zhang Y; Tejomurthula S; Lipzen A; Ng V; Clendinen CS; Tolic N; Grigoriev IV; Tsang A; Mäkelä MR; Snel B; Peng M; de Vries RP;	36547648 BIOLOGY
7	Sperm histone H3 lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction	Anne-Sophie Pepin	35183795 PERFORM
8	Bioinspired facilitation of intrinsically conductive polymers: Mediating intra/extracellular electron transfer and microbial metabolism in denitrification	Guo T; Lu C; Chen Z; Song Y; Li H; Han Y; Hou Y; Zhong Y; Guo J;	35124084 ENCS
9	Altered immunometabolism in adipose tissue: a major contributor to the ageing process?	Delaney KZ; Gillespie ZE; Murphy J; Wang C;	34159597 PERFORM
10	Ghrelin receptor signalling is not required for glucocorticoid-induced obesity in female mice	Silver Z; Abbott-Tate S; Hyland L; Sherratt F; Woodside B; Abizaid A;	34060474 CSBN
11	Caloric restriction creates a metabolic pattern of chronological aging delay that in budding yeast differs from the metabolic design established by two other geroprotectors	Mohammad K; Titorenko VI;	33868583 BIOLOGY
12	Acetyl-CoA regulation, OXPHOS integrity and leptin level are different in females with different onsets of obesity.	Tam BT, Murphy J, Khor N, Morais JA, Santosa S	32808657 PERFORM
13	Mechanisms that Link Chronological Aging to Cellular Quiescence in Budding Yeast.	Mohammad K, Baratang Junio JA, Tafakori T, Orfanos E, Titorenko VI	32630624 BIOLOGY
14	Plasma levels of one-carbon metabolism nutrients in women with anorexia nervosa	Burdo J; Booij L; Kahan E; Thaler L; Israël M; Agellon LB; Nitschmann E; Wykes L; Steiger H;	32427359 PSYCHOLOGY
15	Evolutionary adaptation of Aspergillus niger for increased ferulic acid tolerance.	Lubbers RJM, Liwanag AJ, Peng M, Dilokpimol A, Benoit-Gelber I, de Vries RP	31674709 CSFG
16	Mechanisms by which PE21, an extract from the white willow Salix alba, delays chronological aging in budding yeast.	Medkour Y, Mohammad K, Arlia-Ciommo A, Svistkova V, Dakik P, Mitrofanova D, Rodriguez MEL, Junio JAB, Taifour T, Escudero P, Goltsios FF, Soodbakhsh S, Maalaoui H, Simard É, Titorenko VI	31645900 BIOLOGY
17	Characterization of Phase I and Glucuronide Phase II Metabolites of 17 Mycotoxins Using Liquid Chromatography-High-Resolution Mass Spectrometry	Slobodchikova I; Sivakumar R; Rahman MS; Vuckovic D;	31344861 CBAMS
18	Lithocholic bile acid accumulated in yeast mitochondria orchestrates a development of an anti-aging cellular pattern by causing age-related changes in cellular proteome.	Beach A, Richard VR, Bourque S, Boukh-Viner T, Kyryakov P, Gomez-Perez A, Arlia-Ciommo A, Feldman R, Leonov A, Piano A, Svistkova V, Titorenko VI	25839782 MASSSPEC
19	Some Metabolites Act as Second Messengers in Yeast Chronological Aging.	Mohammad K, Dakik P, Medkour Y, McAuley M, Mitrofanova D, Titorenko VI	29543708 BIOLOGY
20	Caloric restriction delays yeast chronological aging by remodeling carbohydrate and lipid metabolism, altering peroxisomal and mitochondrial functionalities, and postponing the onsets of apoptotic and liponecrotic modes of regulated cell death.	Arlia-Ciommo A, Leonov A, Beach A, Richard VR, Bourque SD, Burstein MT, Kyryakov P, Gomez-Perez A, Koupaki O, Feldman R, Titorenko VI	29662634 BIOLOGY
21	Mechanisms through which lithocholic acid delays yeast chronological aging under caloric restriction conditions.	Arlia-Ciommo A, Leonov A, Mohammad K, Beach A, Richard VR, Bourque SD, Burstein MT, Goldberg AA, Kyryakov P, Gomez-Perez A, Koupaki O, Titorenko VI	30405886 BIOLOGY
22	Reconstituting Plant Secondary Metabolism in Saccharomyces cerevisiae for Production of High-Value Benzylisoquinoline Alkaloids.	Pyne ME, Narcross L, Fossati E, Bourgeois L, Burton E, Gold ND, Martin VJ	27417930 CSFG
23	In vivo α-hydroxylation of a 2-alkylindole antagonist of the OXE receptor for the eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid in monkeys.	Chourey S, Ye Q, Reddy CN, Cossette C, Gravel S, Zeller M, Slobodchikova I, Vuckovic D, Rokach J, Powell WS	28476332 PERFORM
24	Metabolism and pharmacokinetics of a potent N-acylindole antagonist of the OXE receptor for the eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) in rats and monkeys.	Reddy CN, Alhamza H, Chourey S, Ye Q, Gore V, Cossette C, Gravel S, Slobodchikova I, Vuckovic D, Rokach J, Powell WS	29339225 PERFORM
25	The Sexual Dimorphism of Lipid Kinetics in Humans.	Santosa S, Jensen MD	26191040 PERFORM
26	Impaired sensorimotor processing during complex gait precedes behavioral changes in middle-aged adults.	Mitchell T, Starrs F, Soucy JP, Thiel A, Paquette C	30247510 PERFORM

Title:	Metabolism and pharmacokinetics of a potent N-acylindole antagonist of the OXE receptor for the eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) in rats and monkeys.
Authors:	Reddy CN, Alhamza H, Chourey S, Ye Q, Gore V, Cossette C, Gravel S, Slobodchikova I, Vuckovic D, Rokach J, Powell WS
Link:	https://www.ncbi.nlm.nih.gov/pubmed/29339225?dopt=Abstract
DOI:	10.1016/j.ejps.2018.01.021
Publication:	European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Keywords:	5-Lipoxygenase products; 5-Oxo-ETE; Drug metabolism; Eicosanoids; Eosinophils; OXE receptor antagonist;
PMID:	29339225	Category:	Eur J Pharm Sci	Date Added:	2019-05-31
Dept Affiliation:	PERFORM 1 Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology, 150 West University Boulevard, Melbourne, FL 32901-6982, USA. 2 Meakins-Christie Laboratories, Centre for Translational Biology, McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada. 3 Department of Chemistry and Biochemistry and PERFORM Centre, Concordia University, 7141 Sherbrooke St. W., Montréal, QC H4B 1R6, Canada. 4 Meakins-Christie Laboratories, Centre for Translational Biology, McGill University Health Centre, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada. Electronic address: william.powell@mcgill.ca.

Description:

Metabolism and pharmacokinetics of a potent N-acylindole antagonist of the OXE receptor for the eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) in rats and monkeys.

Eur J Pharm Sci. 2018 Mar 30;115:88-99

Authors: Reddy CN, Alhamza H, Chourey S, Ye Q, Gore V, Cossette C, Gravel S, Slobodchikova I, Vuckovic D, Rokach J, Powell WS

Abstract

We previously identified the indole 264 as a potent in vitro antagonist of the human OXE receptor that mediates the actions of the powerful eosinophil chemoattractant 5-oxo-ETE. No antagonists of this receptor are currently commercially available or are being tested in clinical studies. The lack of a rodent ortholog of the OXE receptor has hampered progress in this area because of the unavailability of commonly used mouse or rat animal models. In the present study, we examined the feasibility of using the cynomolgus monkey as an animal model to investigate the efficacy of orally administered 264 in future in vivo studies. We first confirmed that 264 is active in monkeys by showing that it is a potent inhibitor of 5-oxo-ETE-induced actin polymerization and chemotaxis in granulocytes. The major microsomal metabolites of 264 were identified by cochromatography with authentic chemically synthesized standards and LC-MS/MS as its ?2-hydroxy and ?2-oxo derivatives, formed by ?2-oxidation of its hexyl side chain. Small amounts of ?1-oxidation products were also identified. None of these metabolites have substantial antagonist potency. High levels of 264 appeared rapidly in the blood following oral administration to both rats and monkeys, and declined to low levels by 24?h. As with microsomes, its major plasma metabolites in monkeys were ?2-oxidation products. We conclude that the monkey is a suitable animal model to investigate potential therapeutic effects of 264. This, or a related compound with diminished susceptibility to ?2-oxidation, could be a useful therapeutic agent in eosinophilic disorders such as asthma.

PMID: 29339225 [PubMed - indexed for MEDLINE]

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