共 30 条
T-226296: a novel, orally active and selective melanin-concentrating hormone receptor antagonist
被引:175
作者:

Takekawa, S
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Asami, A
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Ishihara, Y
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Terauchi, J
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Kato, K
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Shimomura, Y
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Mori, M
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Murakoshi, H
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Kato, K
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Suzuki, N
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Nishimura, O
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机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan

Fujino, M
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h-index: 0
机构: Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan
机构:
[1] Takeda Chem Ind Ltd, Discovery Res Labs 1, Div Pharmaceut Res, Tsukuba, Ibaraki 3004293, Japan
[2] Med Chem Res Labs 2, Osaka 5328686, Japan
[3] Takeda Chem Ind Ltd, Pharmaceut Res Labs 2, Yodogawa Ku, Osaka 5328686, Japan
关键词:
(MCH) melanin-concentrating hormone;
SLC-1;
receptor;
receptor antagonist;
food intake;
obesity;
D O I:
10.1016/S0014-2999(02)01314-6
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
Through the screening of our in-house chemical compound library, we found a novel melanin-concentrating hormone (MCH) receptor antagonist, T-226296, a (-) enantiomer of N-[6-(dimethylamino)-methyl]-5,6,7,8-tetrahydro-2-naphthalenyl]-4' -fluoro[1,1' -biphenyl]-4-carboxamide. T-226296 exhibited high affinity for cloned human and rat MCH receptors (SLC-1) in receptor binding assays (IC50=5.5 +/- 0.12 nM for human SLC-1; 8.6 +/- 0.32 nM for rat SLC-1). T-226296 had high selectivity over other receptors, including the second subtype of the MCH receptor, SLT (MCH2), transporters and ion channels. In Chinese hamster ovary (CHO) cells expressing human SLC-1, T-226296 reversed the MCH-mediated inhibition of forskolin-stimulated CAMP accumulation, inhibited MCH-induced intracellular Ca2+ increase, and also inhibited MCH-stimulated arachidonic acid release. In rats, oral administration of T-226296 (30 mg/kg) almost completely suppressed the food intake induced by intracerebroventricular injection of MCH. These results clearly indicate that T-226296 is a novel, orally active and selective MCH receptor antagonist that will be promising for further exploring the physiology and pathophysiology of MCH-SLC-1 signaling. (C) 2002 Elsevier Science B.V All rights reserved.
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页码:129 / 135
页数:7
相关论文
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