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PDBsum entry 2ica
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Cell adhesion
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PDB id
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2ica
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References listed in PDB file
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Key reference
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Title
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Discovery and development of 5-[(5s,9r)-9-(4-Cyanophenyl)-3-(3,5-Dichlorophenyl)-1-Methyl-2,4-Dioxo-1,3,7-Triazaspiro[4.4]non-7-Yl-Methyl]-3-Thiophenecarboxylic acid (bms-587101)--A small molecule antagonist of leukocyte function associated antigen-1.
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Authors
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D.Potin,
M.Launay,
F.Monatlik,
P.Malabre,
M.Fabreguettes,
A.Fouquet,
M.Maillet,
E.Nicolai,
L.Dorgeret,
F.Chevallier,
D.Besse,
M.Dufort,
F.Caussade,
S.Z.Ahmad,
D.K.Stetsko,
S.Skala,
P.M.Davis,
P.Balimane,
K.Patel,
Z.Yang,
P.Marathe,
J.Postelneck,
R.M.Townsend,
V.Goldfarb,
S.Sheriff,
H.Einspahr,
K.Kish,
M.F.Malley,
J.D.Dimarco,
J.Z.Gougoutas,
P.Kadiyala,
D.L.Cheney,
R.W.Tejwani,
D.K.Murphy,
K.W.Mcintyre,
X.Yang,
S.Chao,
L.Leith,
Z.Xiao,
A.Mathur,
B.C.Chen,
D.R.Wu,
S.C.Traeger,
M.Mckinnon,
J.C.Barrish,
J.A.Robl,
E.J.Iwanowicz,
S.J.Suchard,
T.G.Dhar.
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Ref.
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J Med Chem, 2006,
49,
6946-6949.
[DOI no: ]
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PubMed id
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Abstract
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LFA-1 (leukocyte function-associated antigen-1), is a member of the
beta2-integrin family and is expressed on all leukocytes. This letter describes
the discovery and preliminary SAR of spirocyclic hydantoin based LFA-1
antagonists that culminated in the identification of analog 8 as a clinical
candidate. We also report the first example of the efficacy of a small molecule
LFA-1 antagonist in combination with CTLA-4Ig in an animal model of transplant
rejection.
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