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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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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Cell adhesion
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Title:
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Cd11a (lfa1) i-domain complexed with bms-587101 aka 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-thiophenecarboxylicacid
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Structure:
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Integrin alpha-l. Chain: a. Fragment: vwfa domain, residues 154-332. Synonym: leukocyte adhesion glycoprotein lfa-1 alpha chain, lfa-1a, leukocyte function-associated molecule 1 alpha chain, cd11a antigen. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: itgal, cd11a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Other_details: minimal media
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Resolution:
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1.56Å
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R-factor:
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0.192
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R-free:
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0.223
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Authors:
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S.Sheriff,H.Einspahr
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Key ref:
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D.Potin
et al.
(2006).
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.
J Med Chem,
49,
6946-6949.
PubMed id:
DOI:
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Date:
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12-Sep-06
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Release date:
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19-Dec-06
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PROCHECK
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Headers
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References
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P20701
(ITAL_HUMAN) -
Integrin alpha-L from Homo sapiens
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Seq:
Struc:
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1170 a.a.
179 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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DOI no:
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J Med Chem
49:6946-6949
(2006)
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PubMed id:
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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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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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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.Cox,
M.Brennan,
and
N.Moran
(2010).
Integrins as therapeutic targets: lessons and opportunities.
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Nat Rev Drug Discov,
9,
804-820.
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D.G.Woodside,
and
P.Vanderslice
(2008).
Cell adhesion antagonists: therapeutic potential in asthma and chronic obstructive pulmonary disease.
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BioDrugs,
22,
85.
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P.M.Fischer
(2008).
Computational chemistry approaches to drug discovery in signal transduction.
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Biotechnol J,
3,
452-470.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
