Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHIZP9)

• DTT Name: Integrin alpha-5 (ITGA5)
• Synonyms: VLA-5; Integrin alpha-F; Integrin alpha-5 light chain; Integrin alpha-5 heavy chain; Fibronectin receptor subunit alpha; FNRA; CD49e antigen; CD49e; CD49 antigen-like family member E
• Gene Name: ITGA5
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Integrin
• UniProt ID: ITA5_HUMAN
• TTD ID: T29879
• Sequence:
  MGSRTPESPLHAVQLRWGPRRRPPLLPLLLLLLPPPPRVGGFNLDAEAPAVLSGPPGSFF
  GFSVEFYRPGTDGVSVLVGAPKANTSQPGVLQGGAVYLCPWGASPTQCTPIEFDSKGSRL
  LESSLSSSEGEEPVEYKSLQWFGATVRAHGSSILACAPLYSWRTEKEPLSDPVGTCYLST
  DNFTRILEYAPCRSDFSWAAGQGYCQGGFSAEFTKTGRVVLGGPGSYFWQGQILSATQEQ
  IAESYYPEYLINLVQGQLQTRQASSIYDDSYLGYSVAVGEFSGDDTEDFVAGVPKGNLTY
  GYVTILNGSDIRSLYNFSGEQMASYFGYAVAATDVNGDGLDDLLVGAPLLMDRTPDGRPQ
  EVGRVYVYLQHPAGIEPTPTLTLTGHDEFGRFGSSLTPLGDLDQDGYNDVAIGAPFGGET
  QQGVVFVFPGGPGGLGSKPSQVLQPLWAASHTPDFFGSALRGGRDLDGNGYPDLIVGSFG
  VDKAVVYRGRPIVSASASLTIFPAMFNPEERSCSLEGNPVACINLSFCLNASGKHVADSI
  GFTVELQLDWQKQKGGVRRALFLASRQATLTQTLLIQNGAREDCREMKIYLRNESEFRDK
  LSPIHIALNFSLDPQAPVDSHGLRPALHYQSKSRIEDKAQILLDCGEDNICVPDLQLEVF
  GEQNHVYLGDKNALNLTFHAQNVGEGGAYEAELRVTAPPEAEYSGLVRHPGNFSSLSCDY
  FAVNQSRLLVCDLGNPMKAGASLWGGLRFTVPHLRDTKKTIQFDFQILSKNLNNSQSDVV
  SFRLSVEAQAQVTLNGVSKPEAVLFPVSDWHPRDQPQKEEDLGPAVHHVYELINQGPSSI
  SQGVLELSCPQALEGQQLLYVTRVTGLNCTTNHPINPKGLELDPEGSLHHQQKREAPSRS
  SASSGPQILKCPEAECFRLRCELGPLHQQESQSLQLHFRVWAKTFLQREHQPFSLQCEAV
  YKALKMPYRILPRQLPQKERQVATAVQWTKAEGSYGVPLWIIILAILFGLLLLGLLIYIL
  YKLGFFKRSLPYGTAMEKAQLKPPATSDA
• Function: It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling. Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen.
• KEGG Pathway:
  Phagosome (hsa04145)
  PI3K-Akt signaling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Hematopoietic cell lineage (hsa04640)
  Regulation of actin cytoskeleton (hsa04810)
  Bacterial invasion of epithelial cells (hsa05100)
  Shigellosis (hsa05131)
  Pertussis (hsa05133)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Hypertrophic cardiomyopathy (HCM) (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Fibronectin matrix formation (R-HSA-1566977)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Integrin cell surface interactions (R-HSA-216083)
  Elastic fibre formation (R-HSA-1566948)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JSM 6427	DM4QIOH	Macular degeneration	9B78.3	Phase 1	[1]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GW-559090	DM1FIN9	Allergic rhinitis	CA08.0	Discontinued in Phase 2	[2]
DW-908e	DMXJ54Z	Allergy	4A80-4A85	Discontinued in Phase 1	[3]
TR-14531	DMH5SA6	Asthma	CA23	Discontinued in Phase 1	[4]
ZD-7349	DM1EB6H	Multiple sclerosis	8A40	Discontinued in Phase 1	[5]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
C(-GRGDfL-)	DMTMJAI	Discovery agent	N.A.	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	2.32E-02	0.19	0.25

References

• [1] An alpha5beta1 integrin inhibitor attenuates glioma growth. Mol Cell Neurosci. 2008 Dec;39(4):579-85.
• [2] Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma. J Leukoc Biol. 2008 January; 83(1): 1-12.
• [3] WO patent application no. 2008,1439,28, Methods and compositions for treating skin conditions.
• [4] US patent application no. US2010278784 (A1), Methods and compositions for treating skin conditions.
• [5] Eosinophil adhesion to cholinergic nerves via ICAM-1 and VCAM-1 and associated eosinophil degranulation. Am J Physiol Lung Cell Mol Physiol. 2002 Jun;282(6):L1279-88.
• [6] Multiple N-methylation by a designed approach enhances receptor selectivity. J Med Chem. 2007 Nov 29;50(24):5878-81.