Very late antigen 4 (VLA4) antagonists as anti-inflammatory agents

被引：85

作者：

Lin, KC ^{[1
]}

Castro, AC

机构：

[1] Biogen Inc, Cambridge Ctr 12, Cambridge, MA 02142 USA

[2] ProScript Inc, Cambridge, MA 02139 USA

来源：

CURRENT OPINION IN CHEMICAL BIOLOGY | 1998年 / 2卷 / 04期

关键词：

D O I：

10.1016/S1367-5931(98)80120-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In recent years antagonists of very late antigen-4 (VLA4, also known as integrin alpha(4)beta(1)) have shown great promise in treating inflammatory disorders in a number of animal models. The most advanced in this endeavor is a humanized anti-alpha(4) antibody, Antegren(R), which is in phase II clinical trials for multiple sclerosis. The first reported small-molecule VLA4 antagonist to advance into clinical trials is currently in phase I as an aerosol for treating asthma. A number of peptides, cyclic peptides and peptidomimetics have been disclosed and are in preliminary stages of development.

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收藏

页码：453 / 457

页数：5

相关论文

共 22 条

[1] Blockade of late-phase airway responses and airway hyperresponsiveness in allergic sheep with a small-molecule peptide inhibitor of VLA-4 [J].

Abraham, WM ;

Ahmed, A ;

Sielczak, MW ;

Narita, M ;

Arrhenius, T ;

Elices, MJ .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1997, 156 (03) :696-703

[2] ALPHA(4)-INTEGRINS MEDIATE ANTIGEN-INDUCED LATE BRONCHIAL RESPONSES AND PROLONGED AIRWAY HYPERRESPONSIVENESS IN SHEEP [J].

ABRAHAM, WM ;

SIELCZAK, MW ;

AHMED, A ;

CORTES, A ;

LAUREDO, IT ;

KIM, J ;

PEPINSKY, B ;

BENJAMIN, CD ;

LEONE, DR ;

LOBB, RR ;

WELLER, PF .

JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (02) :776-787

[3] ADHESION OF HUMAN BASOPHILS, EOSINOPHILS, AND NEUTROPHILS TO INTERLEUKIN 1-ACTIVATED HUMAN VASCULAR ENDOTHELIAL-CELLS - CONTRIBUTIONS OF ENDOTHELIAL-CELL ADHESION MOLECULES [J].

BOCHNER, BS ;

LUSCINSKAS, FW ;

GIMBRONE, MA ;

NEWMAN, W ;

STERBINSKY, SA ;

DERSEANTHONY, CP ;

KLUNK, D ;

SCHLEIMER, RP .

JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (06) :1553-1556

[4]

CARDARELLI PM, 1994, J BIOL CHEM, V269, P18668

[5] MONOCLONAL-ANTIBODIES TO THE INTEGRIN ALPHA-4 SUBUNIT INHIBIT THE MURINE CONTACT HYPERSENSITIVITY RESPONSE [J].

CHISHOLM, PL ;

WILLIAMS, CA ;

LOBB, RR .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (03) :682-688

[6] VCAM-1 ON ACTIVATED ENDOTHELIUM INTERACTS WITH THE LEUKOCYTE INTEGRIN VLA-4 AT A SITE DISTINCT FROM THE VLA-4 FIBRONECTIN BINDING-SITE [J].

ELICES, MJ ;

OSBORN, L ;

TAKADA, Y ;

CROUSE, C ;

LUHOWSKYJ, S ;

HEMLER, ME ;

LOBB, RR .

CELL, 1990, 60 (04) :577-584

[7]

GREENSPOON N, 1994, INT J PEPT PROT RES, V43, P417

[8] LYMPHOID-CELLS RECOGNIZE AN ALTERNATIVELY SPLICED SEGMENT OF FIBRONECTIN VIA THE INTEGRIN RECEPTOR-ALPHA-4-BETA-1 [J].

GUAN, JL ;

HYNES, RO .

CELL, 1990, 60 (01) :53-61

[9] Potent alpha 4 beta 1 peptide antagonists as potential anti-inflammatory agents [J].

Jackson, DY ;

Quan, C ;

Artis, DR ;

Rawson, T ;

Blackburn, B ;

Struble, M ;

Fitzgerald, G ;

Chan, K ;

Mullins, S ;

Burnier, JP ;

Fairbrother, WJ ;

Clark, K ;

Berisini, M ;

Chui, H ;

Renz, M ;

Jones, S ;

Fong, S .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (21) :3359-3368

[10] IDENTIFICATION OF PUTATIVE LIGAND-BINDING SITES OF THE INTEGRIN ALPHA-4-BETA-1 (VLA-4, CD49D/CD29) [J].

KAMATA, T ;

PUZON, W ;

TAKADA, Y .

BIOCHEMICAL JOURNAL, 1995, 305 :945-951