Target Information

Target General Infomation
Target ID
T35640
Former ID
TTDS00444
Target Name
Lymphocyte function-associated antigen 1
Gene Name
ITGAL
Synonyms
CD11a; Integrin alpha-L; LFA-1; LFA-1A; Leukocyte adhesion glycoprotein LFA-1 alpha chain; Leukocyte function associated molecule 1, alpha chain; Lymphocyte Function-associated Antigen-1; ITGAL
Target Type
Successful
Disease Allergic conjunctivitis [ICD9: 204.0, 372.0, 372.14, 995.3; ICD10: C91.0, H10, H10.45, T78.4]
Autoimmune diabetes [ICD10: E08-E13]
Dry eye disease [ICD9: 370.33; ICD10: H16.229]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Psoriasis [ICD9: 696; ICD10: L40]
Renal transplantation [ICD9: 279.5; ICD10: D89.8]
Function
Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes.
Target Validation
T35640
UniProt ID
P20701
Sequence
MKDSCITVMAMALLSGFFFFAPASSYNLDVRGARSFSPPRAGRHFGYRVLQVGNGVIVGA
PGEGNSTGSLYQCQSGTGHCLPVTLRGSNYTSKYLGMTLATDPTDGSILACDPGLSRTCD
QNTYLSGLCYLFRQNLQGPMLQGRPGFQECIKGNVDLVFLFDGSMSLQPDEFQKILDFMK
DVMKKLSNTSYQFAAVQFSTSYKTEFDFSDYVKRKDPDALLKHVKHMLLLTNTFGAINYV
ATEVFREELGARPDATKVLIIITDGEATDSGNIDAAKDIIRYIIGIGKHFQTKESQETLH
KFASKPASEFVKILDTFEKLKDLFTELQKKIYVIEGTSKQDLTSFNMELSSSGISADLSR
GHAVVGAVGAKDWAGGFLDLKADLQDDTFIGNEPLTPEVRAGYLGYTVTWLPSRQKTSLL
ASGAPRYQHMGRVLLFQEPQGGGHWSQVQTIHGTQIGSYFGGELCGVDVDQDGETELLLI
GAPLFYGEQRGGRVFIYQRRQLGFEEVSELQGDPGYPLGRFGEAITALTDINGDGLVDVA
VGAPLEEQGAVYIFNGRHGGLSPQPSQRIEGTQVLSGIQWFGRSIHGVKDLEGDGLADVA
VGAESQMIVLSSRPVVDMVTLMSFSPAEIPVHEVECSYSTSNKMKEGVNITICFQIKSLI
PQFQGRLVANLTYTLQLDGHRTRRRGLFPGGRHELRRNIAVTTSMSCTDFSFHFPVCVQD
LISPINVSLNFSLWEEEGTPRDQRAQGKDIPPILRPSLHSETWEIPFEKNCGEDKKCEAN
LRVSFSPARSRALRLTAFASLSVELSLSNLEEDAYWVQLDLHFPPGLSFRKVEMLKPHSQ
IPVSCEELPEESRLLSRALSCNVSSPIFKAGHSVALQMMFNTLVNSSWGDSVELHANVTC
NNEDSDLLEDNSATTIIPILYPINILIQDQEDSTLYVSFTPKGPKIHQVKHMYQVRIQPS
IHDHNIPTLEAVVGVPQPPSEGPITHQWSVQMEPPVPCHYEDLERLPDAAEPCLPGALFR
CPVVFRQEILVQVIGTLELVGEIEASSMFSLCSSLSISFNSSKHFHLYGSNASLAQVVMK
VDVVYEKQMLYLYVLSGIGGLLLLLLIFIVLYKVGFFKRNLKEKMEAGRGVPNGIPAEDS
EQLASGQEAGDPGCLKPLHEKDSESGGGKD
Structure
1CQP; 1DGQ; 1IJ4; 1LFA; 1MJN; 1MQ8; 1MQ9; 1MQA; 1RD4; 1T0P; 1XDD;1XDG; 1XUO; 1ZON; 1ZOO; 1ZOP; 2ICA; 2K8O; 2M3E; 2O7N; 3BN3; 3BQM; 3BQN; 3E2M; 3EOA; 3EOB; 3F74; 3F78; 3HI6; 3M6F; 3TCX; 4IXD; 1CQP; 1DGQ; 1IJ4; 1LFA; 1MJN; 1MQ8; 1MQ9; 1MQA; 1RD4; 1T0P; 1XDD; 1XDG; 1XUO; 1ZON; 1ZOO; 1ZOP; 2ICA; 2K8O; 2M3E; 2O7N; 3BN3; 3BQM; 3BQN; 3E2M; 3EOA; 3EOB; 3F74; 3F78; 3HI6; 3M6F; 3TCX; 4IXD
Drugs and Mode of Action
Drug(s) Efalizumab Drug Info Approved Psoriasis [537129], [541714]
lifitegrast Drug Info Approved Dry eye disease [889440]
SAR-1118 Drug Info Phase 3 Allergic conjunctivitis [523596], [542538]
Efalizumab Drug Info Phase 2 Renal transplantation [537129], [541714]
Cytolin Drug Info Preclinical Human immunodeficiency virus infection [550574]
IC-747 Drug Info Discontinued in Phase 2 Psoriasis [547348]
Inhibitor A-286982 Drug Info [531049]
BMS-587101 Drug Info [530861]
LFA703 Drug Info [551393]
SAR-1118 Drug Info [532142]
Antagonist IC-747 Drug Info [551183]
Modulator Leukotoxin Drug Info [543632]
lifitegrast Drug Info [889440]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Rap1 signaling pathway
Cell adhesion molecules (CAMs)
Natural killer cell mediated cytotoxicity
Leukocyte transendothelial migration
Regulation of actin cytoskeleton
Malaria
Staphylococcus aureus infection
HTLV-I infection
Epstein-Barr virus infection
Rheumatoid arthritis
Viral myocarditis
NetPath Pathway TCR Signaling Pathway
RANKL Signaling Pathway
PANTHER Pathway Inflammation mediated by chemokine and cytokine signaling pathway
Integrin signalling pathway
Pathway Interaction Database Integrin family cell surface interactions
Beta2 integrin cell surface interactions
CXCR3-mediated signaling events
Reactome Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Cell surface interactions at the vascular wall
Integrin cell surface interactions
WikiPathways Focal Adhesion
Integrin-mediated Cell Adhesion
Integrin cell surface interactions
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Cell surface interactions at the vascular wall
References
Ref 523596ClinicalTrials.gov (NCT01421498) Safety and Efficacy Study of SAR 1118 to Treat Dry Eye. U.S. National Institutes of Health.
Ref 537129New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
Ref 541714(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6593).
Ref 542538(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7533).
Ref 547348Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015378)
Ref 550574Clinical pipeline report, company report or official report of CytoDyn Inc.
Ref 8894402016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. doi: 10.1038/nrd.2017.14.
Ref 528611Cytokine-induced phagocyte adhesion to human mesangial cells: role of CD11/CD18 integrins and ICAM-1. Am J Physiol. 1991 Dec;261(6 Pt 2):F1071-9.
Ref 530861J Med Chem. 2010 May 13;53(9):3814-30.Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): structure-activity relationships leading to the identification of 6-((5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic acid (BMS-688521).
Ref 531049Bioorg Med Chem Lett. 2010 Sep 1;20(17):5269-73. Epub 2010 Jul 23.Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists.
Ref 532142Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118). J Ocul Pharmacol Ther. 2013 May;29(4):395-402.
Ref 537313Successful therapy of discoid lupus erythematosus with efalizumab.. Hautarzt. 2009 May 14. Epub ahead of print.
Ref 543632(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2451).
Ref 551183HECA-452+ T Cells Migrate Through Superficial Vascular Plexus but Not Through Deep Vascular Plexus Endothelium. Journal of Investigative Dermatology. 04/1997; 108(3):343-8.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 8894402016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. doi: 10.1038/nrd.2017.14.

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