BIIE0246:: A selective and high affinity neuropeptide YY2 receptor antagonist

被引：168

作者：

Doods, H ^{[1
]}

Gaida, W ^{[1
]}

Wieland, HA ^{[1
]}

Dollinger, H ^{[1
]}

Schnorrenberg, G ^{[1
]}

Esser, F ^{[1
]}

Engel, W ^{[1
]}

Eberlein, W ^{[1
]}

Rudolf, K ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharma GmbH & Co KG, D-88397 Biberach, Germany

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1999年 / 384卷 / 2-3期

关键词：

neuropeptide Y; neuropeptide YY2; receptor antagonist; BIIE0246;

D O I：

10.1016/S0014-2999(99)00650-0

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The in vitro biological characterisation of the first potent and selective non-peptide neuropeptide Y Y-2 receptor antagonist, (S)-N-2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamid (BIIE0246) is reported. BIIE0246 displaced [I-125]neuropeptide Y with high affinity (IC50 = 3.3 nM) from the human neuropeptide Y Y-2 receptor and proved to be highly selective. BIIE0246 displayed antagonistic properties and thus represents the first selective non-peptide neuropeptide Y Y-2 receptor antagonist. (C) 1999 Elsevier Science B.V. All rights reserved.

引用

页码：R3 / R5

页数：3

共 8 条

[1] Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor [J].

Criscione, L ;

Rigollier, P ;

Batzl-Hartmann, C ;

Rüeger, H ;

Stricker-Krongrad, A ;

Wyss, P ;

Brunner, L ;

Whitebread, S ;

Yamaguchi, Y ;

Gerald, C ;

Heurich, RO ;

Walker, MW ;

Chiesi, M ;

Schilling, W ;

Hofbauer, KG ;

Levens, N .

JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (12) :2136-2145

[2] DIFFERENT NEUROPEPTIDE-Y RECEPTOR SUBTYPES IN RAT AND RABBIT VAS-DEFERENS [J].

DOODS, HN ;

KRAUSE, J .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 204 (01) :101-103

[3] EXPRESSION CLONING AND PHARMACOLOGICAL CHARACTERIZATION OF A HUMAN HIPPOCAMPAL NEUROPEPTIDE-Y PEPTIDE YY Y2 RECEPTOR SUBTYPE [J].

GERALD, C ;

WALKER, MW ;

VAYSSE, PJJ ;

HE, CG ;

BRANCHEK, TA ;

WEINSHANK, RL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (45) :26758-26761

[4] A receptor subtype involved in neuropeptide-Y-induced food intake [J].

Gerald, C ;

Walker, MW ;

Criscione, L ;

Gustafson, EL ;

BatzlHartmann, C ;

Smith, KE ;

Vaysse, P ;

Durkin, MM ;

Laz, TM ;

Linemeyer, DL ;

Schaffhauser, AO ;

Whitebread, S ;

Hofbauer, KG ;

Taber, RI ;

Branchek, TA ;

Weinshank, RL .

NATURE, 1996, 382 (6587) :168-171

[5] Characterization of a selective antagonist of neuropeptide Y at the Y2 receptor - Synthesis and pharmacological evaluation of a Y2 antagonist [J].

Grouzmann, E ;

Buclin, T ;

Martire, M ;

Cannizzaro, C ;

Dorner, B ;

Razaname, A ;

Mutter, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (12) :7699-7706

[6]

Michel MC, 1998, PHARMACOL REV, V50, P143

[7] THE FIRST HIGHLY POTENT AND SELECTIVE NONPEPTIDE NEUROPEPTIDE-Y Y-1-RECEPTOR ANTAGONIST - BIBP3226 [J].

RUDOLF, K ;

EBERLEIN, W ;

ENGEL, W ;

WIELAND, HA ;

WILLIM, KD ;

ENTZEROTH, M ;

WIENEN, W ;

BECKSICKINGER, AG ;

DOODS, HN .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1994, 271 (2-3) :R11-R13

[8] Subtype selectivity of the novel nonpeptide neuropeptide Y Y1 receptor antagonist BIBO 3304 and its effect on feeding in rodents [J].

Wieland, HA ;

Engel, W ;

Eberlein, W ;

Rudolf, K ;

Doods, HN .

BRITISH JOURNAL OF PHARMACOLOGY, 1998, 125 (03) :549-555

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