PERFORM Publications

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Title		Authors	PubMed ID
1	Metabolism of anti-inflammatory OXE (oxoeicosanoid) receptor antagonists by nonhuman primates	Cossette C; Chourey S; Ye Q; Reddy CN; Wang R; Poulet S; Slobodchikova I; Vuckovic D; Rokach J; Powell WS;	35158054 PERFORM
2	Novel highly potent OXE receptor antagonists with prolonged plasma lifetimes that are converted to active metabolites in vivo in monkeys.	Ye Q, Chourey S, Reddy CN, Wang R, Cossette C, Gravel S, Slobodchikova I, Vuckovic D, Rokach J, Powell WS	31655025 PERFORM
3	Pharmacokinetics and Metabolism of Selective Oxoeicosanoid (OXE) Receptor Antagonists and Their Effects on 5-Oxo-6,8,11,14-eicosatetraenoic Acid (5-Oxo-ETE)-Induced Granulocyte Activation in Monkeys.	Cossette C, Chourey S, Ye Q, Nagendra Reddy C, Gore V, Gravel S, Slobodchikova I, Vuckovic D, Rokach J, Powell WS	27766872 PERFORM
4	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
5	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
6	Corrigendum to "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" [Biochem. Pharmacol. 138 (2017) 107-118].	Chourey S, Ye Q, Reddy CN, Cossette C, Gravel S, Zeller M, Slobodchikova I, Vuckovic D, Rokach J, Powell WS	29754018 PERFORM
7	Novel Highly Potent and Metabolically Resistant Oxoeicosanoid (OXE) Receptor Antagonists That Block the Actions of the Granulocyte Chemoattractant 5-Oxo-6,8,11,14-Eicosatetraenoic Acid (5-oxo-ETE).	Chourey S, Ye Q, Reddy CN, Wang R, Cossette C, Gravel S, Slobodchikova I, Vuckovic D, Rokach J, Powell WS	29972644 PERFORM

Title:	Pharmacokinetics and Metabolism of Selective Oxoeicosanoid (OXE) Receptor Antagonists and Their Effects on 5-Oxo-6,8,11,14-eicosatetraenoic Acid (5-Oxo-ETE)-Induced Granulocyte Activation in Monkeys.
Authors:	Cossette C, Chourey S, Ye Q, Nagendra Reddy C, Gore V, Gravel S, Slobodchikova I, Vuckovic D, Rokach J, Powell WS
Link:	https://www.ncbi.nlm.nih.gov/pubmed/27766872?dopt=Abstract
DOI:	10.1021/acs.jmedchem.6b00895
Publication:	Journal of medicinal chemistry
Keywords:
PMID:	27766872	Category:	J Med Chem	Date Added:	2019-05-31
Dept Affiliation:	PERFORM 1 Meakins-Christie Laboratories, Centre for Translational Biology, McGill University Health Centre , 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1, Canada. 2 Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901-6982, United States. 3 Department of Chemistry and Biochemistry and PERFORM Centre, Concordia University , 7141 Sherbrooke Street West, Montréal, Quebec H4B 1R6, Canada.

Description:

Pharmacokinetics and Metabolism of Selective Oxoeicosanoid (OXE) Receptor Antagonists and Their Effects on 5-Oxo-6,8,11,14-eicosatetraenoic Acid (5-Oxo-ETE)-Induced Granulocyte Activation in Monkeys.

J Med Chem. 2016 11 23;59(22):10127-10146

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

Abstract

The potent eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a 5-lipoxygenase product that acts via the selective OXE receptor, which is present in many species, but not rodents. We previously reported that the indole 230 is a potent human OXE receptor antagonist. The objective of the present study was to determine whether the monkey would be a suitable animal model to investigate its pharmaceutical potential. We found that monkey leukocytes synthesize and respond to 5-oxo-ETE and that 230 is a potent antagonist of the OXE receptor in monkey eosinophils. Pharmacokinetic studies revealed that 230 appears rapidly in the blood following oral administration. Using chemically synthesized standards, we identified the major microsomal and plasma metabolites of 230 as products of ?2-hydroxylation of the alkyl side chain. These studies demonstrate that the monkey is a promising animal model to investigate the drug potential of OXE receptor antagonists.

PMID: 27766872 [PubMed - indexed for MEDLINE]

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