Selective α4β7 integrin antagonists and their potential as antiinflammatory agents

Journal of Medicinal Chemistry

Volumn 45, Issue 16, 2002, Pages 3451-3457

  Dubree, Nathan J P ^a   Artis, Dean R ^a   Castanedo, Georgette ^a   Marsters, James ^a   Sutherlin, Daniel ^a   Caris, Lisa ^a   Clark, Kevin ^a   Keating, Susan M ^a   Beresini, Maureen H ^a   Chiu, Henry ^a   Fong, Sherman ^a   Lowman, Henry B ^a   Skelton, Nicholas J ^a   Jackson, David Y ^a  

^a GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA4 BETA7 INTEGRIN ANTAGONIST; ALPHA4 INTEGRIN; ANTIINFLAMMATORY AGENT; BETA7 INTEGRIN; INTEGRIN; MONOCLONAL ANTIBODY; MUCOSAL ADDRESSIN CELL ADHESION MOLECULE 1; PEPTIDE LIBRARY; UNCLASSIFIED DRUG; ALANINE; CELL ADHESION MOLECULE; CYCLOPEPTIDE; HOMING RECEPTOR; IMMUNOGLOBULIN; INTEGRIN ALPHA4BETA7; MADCAM1 PROTEIN, HUMAN; MADCAM1 PROTEIN, MOUSE; MUCOPROTEIN; NONSTEROID ANTIINFLAMMATORY AGENT; OLIGOPEPTIDE; PEPTIDE FRAGMENT; VASCULAR CELL ADHESION MOLECULE 1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; AUTOIMMUNE DISEASE; B LYMPHOCYTE; BINDING AFFINITY; COMPETITIVE INHIBITION; CONTROLLED STUDY; CROHN DISEASE; DIGESTIVE SYSTEM INFLAMMATION; DRUG POTENCY; DRUG SELECTIVITY; GASTROINTESTINAL TRACT; HEPATITIS C; LEUKOCYTE; MOLECULAR INTERACTION; MOUSE; NONHUMAN; PROTEIN EXPRESSION; STRUCTURE ACTIVITY RELATION; T LYMPHOCYTE; ULCERATIVE COLITIS; AMINO ACID SUBSTITUTION; ANIMAL; CHEMISTRY; COLITIS; DRUG ANTAGONISM; DRUG EFFECT; ENZYME LINKED IMMUNOSORBENT ASSAY; INTESTINE; LYMPH NODE; LYMPHOCYTE; MOLECULAR MIMICRY; NEUTROPHIL CHEMOTAXIS; PATHOLOGY; SYNTHESIS;

ALANINE; AMINO ACID SUBSTITUTION; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CELL ADHESION MOLECULES; CHEMOTAXIS, LEUKOCYTE; COLITIS; ENZYME-LINKED IMMUNOSORBENT ASSAY; IMMUNOGLOBULINS; INTEGRINS; INTESTINES; LYMPH NODES; LYMPHOCYTES; MICE; MOLECULAR MIMICRY; MUCOPROTEINS; OLIGOPEPTIDES; PEPTIDE FRAGMENTS; PEPTIDE LIBRARY; PEPTIDES, CYCLIC; RECEPTORS, LYMPHOCYTE HOMING; STRUCTURE-ACTIVITY RELATIONSHIP; VASCULAR CELL ADHESION MOLECULE-1;

EID: 0036667327     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020033k     Document Type: Article

References (49)

1. Traffic signals of lymphocyte recirculation and leukocyte emigration: The multistep paradigm
2. Role of α4 integrins in lymphocyte homing to mucosal tissues in vivo
3. Lymphocyte homing and homeostasis
4. T-Cell function and migration
5. Autoimmune diseases
6. Mechanisms of disease: Molecular mimicry and autoimmunity
7. α4 Integrin-dependent emigration of monocytes
8. α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1
9. Expression and function of the MadCAM-1 receptor, integrin α4β7 on human leukocytes
10. Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells
11. VCAM-1 on activated endothelium interact with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site
12. Activated endothelium binds lymphocytes through a novel binding site in the alternatively spliced domain of VCAM-1
13. MAdCAM-1 has homology to immunoglobulin and mucin-like adhesion receptors and to IgA1
14. Identification of a key integrin-binding sequence in VCAM-1 homologous to the LDV active site in fibronectin
15. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1): Its binding motif for α4β7 and role in experimental colitis
16. Similar but nonidentical amino acid residues on VCAM-1 are involved in the interaction with α4β1 and α4β7 under different activity states
17. Structural requirements for adhesion of soluble recombinant murine VCAM-1 to α4β1
18. Mucosal addressin cell adhesion molecule 1: A structural and functional analysis demarcates the integrin binding motif
19. VCAM-1/α4-integrin adhesion pathway: Therapeutic target for allergic inflammatory disorders
20. Mutational analysis of MAdCAM/α4β7 interactions reveals significant binding determinants in both the first and second immunoglobulin domains
21. Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 å resolution
22. The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition
23. The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule-1 (VCAM-1): A cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-α4 integrin interaction
24. Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and chronic inflammation
25. VCAM-1 expression on human dermal microvascular endothelial cells is directly and specifically up-regulated by substance P
26. Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) demonstrates structural and functional similarities to the α4β7-integrin binding domains of murine MAdCAM-1, but extreme divergence of mucin-like sequences
27. Expression of lymphocyte-endothelial receptor-ligand pairs, α4β7/MAdCAM-1 and OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease
28. Expression of the mucosal vascular addressin, MAdCAM-1, in inflammatory liver disease
29. Novel therapeutics in inflammatory bowell disease
30. An ascending dose trial of a humanized anti-α4β7 antibody in ulcerative colitis
31. Differential requirements for α4 integrins during fetal and adult hematopoiesis
32. α4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo
33. Design and synthesis of potent and selective α4β7 integrin antagonists
34. Mapping the binding epitopes of IGF-1 and a phage-library derived peptide that inhibits IGFBP-1 binding to insulin-like growth factor
35. Phage display for selection of novel binding peptides
36. Molecular mimics of insulin-like growth factor 1 (IGF-1) for inhibiting IGF-1: IGF-binding protein interactions
37. Potent α4β1 peptide antagonists as potential anti-inflammatory agents
38. Selection of peptides binding to the α5β1 integrin from phage display library
39. Cyclic RGD peptide analogs as antiplatelet antithrombotics
40. A 125/115-kDa cell surface receptor specific for vitronectin interacts with the RGD adhesion sequence derived from vibronectin
41. Role of VCAM-1/VLA-4 and ICAM-1/LFA-1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue
42. MAdCAM mediates lymphocyte-endothelial cell adhesion in a murine model of chronic colitis
43. VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice
44. Amelioration of murine experimental colitis by inhibition of mucosal addressin cell adhesion molecule-1
45. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Its binding motif for α4β7 and role in experimental colitis
46. Peptide synthesis using FMOC protection
47. Wang resin peptide synthesis
48. Cytokine and adhesion molecule expression in SCID mice reconstituted with CD4+ T cells
49. Cytokine and endothelial cell adhesion molecule expression in interleukin-10-deficient mice