A simple in vitro assay for assessing the reactivity of nitrile containing compounds

被引：56

作者：

MacFaul, Philip A. ^{[1
]}

Morley, Andrew D. ^{[1
]}

Crawford, James J. ^{[1
]}

机构：

[1] AstraZeneca, Mereside, Macclesfield SK10 4TG, Cheshire, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 04期

关键词：

Nitriles; Glutathione; Cysteine; Benchmarking; GLUTATHIONE TRANSFERASES; CATHEPSIN-K; METABOLIC-ACTIVATION; CATALYTIC MECHANISM; AQUEOUS-SOLUTIONS; THIOLS; INHIBITORS; CYSTEINE; POTENT;

D O I：

10.1016/j.bmcl.2008.12.105

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A quantitative assay involving the reaction of nitriles with glutathione and cysteine has been used as a simple in vitro screen to assess potential toxicity risk of candidate compounds in drug discovery. Studies have indicated that, when benchmarked with selected compounds, the reaction of the nitriles with glutathione can provide a useful tool for deciding whether or not to progress compounds in the absence of radiolabelling studies. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1136 / 1138

页数：3

共 22 条

[1] KINETICS ANALYSIS OF THE DECAY OF PHENYLHYDRAZONO-PROPANEDINITRILE ADDITION-PRODUCTS WITH THIOLS IN AQUEOUS-SOLUTIONS
ANTALIK, M
STURDIK, E
PODHRADSKY, D
POLEKOVA, I
DROBNICA, I
[J]. COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 1989, 54 (12) : 3387 - 3396
[2] Structure, catalytic mechanism, and evolution of the glutathione transferases
Armstrong, RN
[J]. CHEMICAL RESEARCH IN TOXICOLOGY, 1997, 10 (01) : 2 - 18
[3] Clarke ED, 1998, PESTIC SCI, V54, P385, DOI 10.1002/(SICI)1096-9063(199812)54:4<385::AID-PS842>3.0.CO
[4] 2-C
[5] IONIZATION OF CYSTEINE IN AQUEOUS SOLUTIONS .1. NET-IONIZATION CONSTANTS
COATES, E
MARSDEN, C
RIGG, B
[J]. TRANSACTIONS OF THE FARADAY SOCIETY, 1969, 65 (555P): : 863 - &
[6] Engineering nitrile hydratase activity into a cysteine protease by a single mutation
Dufour, E
Storer, AC
Menard, R
[J]. BIOCHEMISTRY, 1995, 34 (50) : 16382 - 16388
[7] Drug-protein adducts: An industry perspective on minimizing the potential for drug bioactivation in drug discovery and development
Evans, DC
Watt, AP
Nicoll-Griffith, DA
Baillie, TA
[J]. CHEMICAL RESEARCH IN TOXICOLOGY, 2004, 17 (01) : 3 - 16
[8] Novel, nonpeptidic cyanamides as potent and reversible inhibitors of human cathepsins K and L
Falgueyret, JP
Oballa, RM
Okamoto, O
Wesolowski, G
Aubin, Y
Rydzewski, RM
Prasit, P
Riendeau, D
Rodan, SB
Percival, MD
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (01) : 94 - 104
[9] Role of the glutamyl α-carboxylate of the substrate glutathione in the catalytic mechanism of human glutathione transferase A1-1
Gustafsson, A
Pettersson, PL
Grehn, L
Jemth, P
Mannervik, B
[J]. BIOCHEMISTRY, 2001, 40 (51) : 15835 - 15845
[10] REVERSIBLE COVALENT BINDING OF PEPTIDE NITRILES TO PAPAIN
HANZLIK, RP
ZYGMUNT, J
MOON, JB
[J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1990, 1035 (01) : 62 - 70

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