Target Information
| Target General Information | Top | |||||
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| Target ID |
T35640
(Former ID: TTDS00444)
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| Target Name |
Integrin alpha-L (ITGAL)
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| Synonyms |
Lymphocyte Function-associated Antigen-1; Leukocyte function-associated molecule 1 alpha chain; Leukocyte function associated molecule 1, alpha chain; Leukocyte adhesion glycoprotein LFA-1 alpha chain; LFA-1A; LFA-1; CD11a; CD11 antigen-like family member A
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| Gene Name |
ITGAL
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Psoriasis [ICD-11: EA90] | |||||
| 2 | Visual system disease [ICD-11: 9E1Z] | |||||
| Function |
Integrin ITGAL/ITGB2 is a receptor for F11R. Integin ITGAL/ITGB2 is a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. 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. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Required for generation of common lymphoid progenitor cells in bone marrow, indicating a role in lymphopoiesis. Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages. Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4.
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| BioChemical Class |
Integrin
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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 Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T91F6Z | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Efalizumab | Drug Info | Approved | Psoriasis vulgaris | [2], [3] | |
| 2 | lifitegrast | Drug Info | Approved | Dry eye disease | [4] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | BMS-587101 | Drug Info | Discontinued in Phase 2 | Psoriasis vulgaris | [5] | |
| 2 | IC-747 | Drug Info | Discontinued in Phase 2 | Psoriasis vulgaris | [6] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | Cytolin | Drug Info | Preclinical | Human immunodeficiency virus infection | [7] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | lifitegrast | Drug Info | [1], [4] | |||
| 2 | Leukotoxin | Drug Info | [13] | |||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | BMS-587101 | Drug Info | [9] | |||
| 2 | A-286982 | Drug Info | [12] | |||
| 3 | LFA703 | Drug Info | [14] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | IC-747 | Drug Info | [10] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Corneal inflammation is inhibited by the LFA-1 antagonist, lifitegrast (SAR 1118). J Ocul Pharmacol Ther. 2013 May;29(4):395-402. | |||||
| REF 2 | URL: 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 3 | New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21. | |||||
| REF 4 | 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76. | |||||
| REF 5 | Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.Nat Rev Drug Discov. 2016 Aug;15(8):533-50. | |||||
| REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015378) | |||||
| REF 7 | Clinical pipeline report, company report or official report of CytoDyn Inc. | |||||
| REF 8 | [Successful therapy of discoid lupus erythematosus with efalizumab]. Hautarzt. 2010 Mar;61(3):246-9. | |||||
| REF 9 | Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): structure-activity relationships leading to the identification of 6-(... J Med Chem. 2010 May 13;53(9):3814-30. | |||||
| REF 10 | HECA-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 11 | 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 12 | Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5269-73. | |||||
| REF 13 | URL: 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 14 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
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