Species selectivity of small-molecular antagonists for the CCR5 chemokine receptor

被引：22

作者：

Saita, Yuji

Kondo, Mitsuhiro

Shimizu, Yasuaki

机构：

[1] Astellas Pharma Inc, Inst Drug Discovery Res, Mol Med Res Labs, Tsukuba, Ibaraki 3058585, Japan

[2] Astellas Pharma Inc, Inst Drug Discovery Res, Pharmacol Res Labs, Osaka 5320031, Japan

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2007年 / 7卷 / 12期

关键词：

chemokines; small-molecular antagonist; species selectivity;

D O I：

10.1016/j.intimp.2007.07.019

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The species selectivity of four structurally different compounds, SCH-351125, E-913, TAK-779 and UK-427857 has been examined using cloned human, rhesus, and mouse CCR5 receptors. SCH-351125 and E-913 potently inhibited the binding of [(125) I]-CCL3 to human CCR5, but their inhibitory activities against rhesus CCR5 were more than 10-fold weaker. In contrast, TAK-779 and UK-427857 inhibited binding to human and rhesus CCR5 with similar potency. The inhibitory activities of all four compounds against mice CCR5 receptors were weak. The inhibitory activities of the CCR5 antagonists in the [I-125]-CCL3 binding assay agreed well with those induced by CCL3 in the intracellular calcium ([Ca2+](i)) elevation assay. Mutational analysis of the human CCR5 receptor showed that its Ile198 component plays a critical role in the inhibitory activities of both SCH-351125 and E-913, but not that of TAK-779 or UK-427857. These results provide a structural basis for understanding how specific antagonists interact with CCR5, and will aid the process of creating new, improved CCR5 antagonists. (C) 2007 Elsevier B.V. All rights reserved.

引用

页码：1528 / 1534

页数：7

共 30 条

[1] A novel small-molecule compound targeting CCR5 and CXCR3 prevents acute and chronic allograft rejection [J].

Akashi, S ;

Sho, M ;

Kashizuka, H ;

Hamada, K ;

Ikeda, N ;

Kuzumoto, Y ;

Tsurui, Y ;

Nomi, T ;

Mizuno, T ;

Kanehiro, H ;

Hisanaga, M ;

Ko, S ;

Nakajima, Y .

TRANSPLANTATION, 2005, 80 (03) :378-384

[2] CC CKRS: A RANTES, MIP-1 alpha, MIP-1 beta receptor as a fusion cofactor for macrophage-tropic HIV-1 [J].

Alkhatib, G ;

Combadiere, C ;

Broder, CC ;

Feng, Y ;

Kennedy, PE ;

Murphy, PM ;

Berger, EA .

SCIENCE, 1996, 272 (5270) :1955-1958

[3] A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity [J].

Baba, M ;

Nishimura, O ;

Kanzaki, N ;

Okamoto, M ;

Sawada, H ;

Iizawa, Y ;

Shiraishi, M ;

Aramaki, Y ;

Okonogi, K ;

Ogawa, Y ;

Meguro, K ;

Fujino, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (10) :5698-5703

[4] The differential sensitivity of human and rhesus macaque CCR5 to small-molecule inhibitors of human immunodeficiency virus type 1 entry is explained by a single amino acid difference and suggests a mechanism of action for these inhibitors [J].

Billick, E ;

Seibert, C ;

Pugach, P ;

Ketas, T ;

Trkola, A ;

Endres, MJ ;

Murgolo, NJ ;

Coates, E ;

Reyes, GR ;

Baroudy, BM ;

Sakmar, TP ;

Moore, JP ;

Kuhmann, SE .

JOURNAL OF VIROLOGY, 2004, 78 (08) :4134-4144

[5] Molecular cloning and functional expression of murine JE (Monocyte chemoattractant protein 1) and murine macrophage inflammatory protein la receptors - Evidence for two closely linked C-C chemokine receptors on chromosome 9 [J].

Boring, L ;

Gosling, J ;

Monteclaro, FS ;

Lusis, AJ ;

Tsou, CL ;

Charo, IF .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (13) :7551-7558

[6] The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates [J].

Choe, H ;

Farzan, M ;

Sun, Y ;

Sullivan, N ;

Rollins, B ;

Ponath, PD ;

Wu, LJ ;

Mackay, CR ;

LaRosa, G ;

Newman, W ;

Gerard, N ;

Gerard, C ;

Sodroski, J .

CELL, 1996, 85 (07) :1135-1148

[7] Identification of a major co-receptor for primary isolates of HIV-1 [J].

Deng, HK ;

Liu, R ;

Ellmeier, W ;

Choe, S ;

Unutmaz, D ;

Burkhart, M ;

DiMarzio, P ;

Marmon, S ;

Sutton, RE ;

Hill, CM ;

Davis, CB ;

Peiper, SC ;

Schall, TJ ;

Littman, DR ;

Landau, NR .

NATURE, 1996, 381 (6584) :661-666

[8] Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity [J].

Dorr, P ;

Westby, M ;

Dobbs, S ;

Griffin, P ;

Irvine, B ;

Macartney, M ;

Mori, J ;

Rickett, G ;

Smith-Burchnell, C ;

Napier, C ;

Webster, R ;

Armour, D ;

Price, D ;

Stammen, B ;

Wood, A ;

Perros, M .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (11) :4721-4732

[9]

Este Jose A, 2002, Curr Opin Investig Drugs, V3, P379

[10] CC chemokine receptor 5 and renal-transplant survival [J].

Fischereder, M ;

Luckow, B ;

Hocher, B ;

Wüthrich, RP ;

Rothenpieler, U ;

Schneeberger, H ;

Panzer, U ;

Stahl, RAK ;

Hauser, IA ;

Budde, K ;

Neumayer, HH ;

Krämer, BK ;

Land, W ;

Schlöndorff, D .

LANCET, 2001, 357 (9270) :1758-1761

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