Target Information
Target General Infomation | |||||
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Target ID |
T35640
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Former ID |
TTDS00444
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Target Name |
Lymphocyte function-associated antigen 1
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Gene Name |
ITGAL
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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
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Target Type |
Successful
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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.
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Target Validation |
T35640
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UniProt ID | |||||
Sequence |
MKDSCITVMAMALLSGFFFFAPASSYNLDVRGARSFSPPRAGRHFGYRVLQVGNGVIVGA
PGEGNSTGSLYQCQSGTGHCLPVTLRGSNYTSKYLGMTLATDPTDGSILACDPGLSRTCD QNTYLSGLCYLFRQNLQGPMLQGRPGFQECIKGNVDLVFLFDGSMSLQPDEFQKILDFMK DVMKKLSNTSYQFAAVQFSTSYKTEFDFSDYVKRKDPDALLKHVKHMLLLTNTFGAINYV ATEVFREELGARPDATKVLIIITDGEATDSGNIDAAKDIIRYIIGIGKHFQTKESQETLH KFASKPASEFVKILDTFEKLKDLFTELQKKIYVIEGTSKQDLTSFNMELSSSGISADLSR GHAVVGAVGAKDWAGGFLDLKADLQDDTFIGNEPLTPEVRAGYLGYTVTWLPSRQKTSLL ASGAPRYQHMGRVLLFQEPQGGGHWSQVQTIHGTQIGSYFGGELCGVDVDQDGETELLLI GAPLFYGEQRGGRVFIYQRRQLGFEEVSELQGDPGYPLGRFGEAITALTDINGDGLVDVA VGAPLEEQGAVYIFNGRHGGLSPQPSQRIEGTQVLSGIQWFGRSIHGVKDLEGDGLADVA VGAESQMIVLSSRPVVDMVTLMSFSPAEIPVHEVECSYSTSNKMKEGVNITICFQIKSLI PQFQGRLVANLTYTLQLDGHRTRRRGLFPGGRHELRRNIAVTTSMSCTDFSFHFPVCVQD LISPINVSLNFSLWEEEGTPRDQRAQGKDIPPILRPSLHSETWEIPFEKNCGEDKKCEAN LRVSFSPARSRALRLTAFASLSVELSLSNLEEDAYWVQLDLHFPPGLSFRKVEMLKPHSQ IPVSCEELPEESRLLSRALSCNVSSPIFKAGHSVALQMMFNTLVNSSWGDSVELHANVTC NNEDSDLLEDNSATTIIPILYPINILIQDQEDSTLYVSFTPKGPKIHQVKHMYQVRIQPS IHDHNIPTLEAVVGVPQPPSEGPITHQWSVQMEPPVPCHYEDLERLPDAAEPCLPGALFR CPVVFRQEILVQVIGTLELVGEIEASSMFSLCSSLSISFNSSKHFHLYGSNASLAQVVMK VDVVYEKQMLYLYVLSGIGGLLLLLLIFIVLYKVGFFKRNLKEKMEAGRGVPNGIPAEDS EQLASGQEAGDPGCLKPLHEKDSESGGGKD |
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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
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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] | |
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 523596 | ClinicalTrials.gov (NCT01421498) Safety and Efficacy Study of SAR 1118 to Treat Dry Eye. U.S. National Institutes of Health. | ||||
Ref 537129 | New 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 528611 | Cytokine-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 530861 | J 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 531049 | Bioorg 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 532142 | Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118). J Ocul Pharmacol Ther. 2013 May;29(4):395-402. | ||||
Ref 537313 | Successful 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). |
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