Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTH4QIS)

• DTT Name: Integrin alpha-5/beta-1 (ITGA5/B1)
• Synonyms: alpha(5)beta(1) integrin; Alpha 5 beta 1 integrin
• Gene Name: ITGA5-ITGB1
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Lung cancer [ICD-11: 2C25]
  Renal cell carcinoma [ICD-11: 2C90]
  Melanoma [ICD-11: 2C30]
• BioChemical Class: Integrin
• UniProt ID: ITA5_HUMAN-ITB1_HUMAN
• TTD ID: T88806
• Sequence:
  MNLQPIFWIGLISSVCCVFAQTDENRCLKANAKSCGECIQAGPNCGWCTNSTFLQEGMPT
  SARCDDLEALKKKGCPPDDIENPRGSKDIKKNKNVTNRSKGTAEKLKPEDITQIQPQQLV
  LRLRSGEPQTFTLKFKRAEDYPIDLYYLMDLSYSMKDDLENVKSLGTDLMNEMRRITSDF
  RIGFGSFVEKTVMPYISTTPAKLRNPCTSEQNCTSPFSYKNVLSLTNKGEVFNELVGKQR
  ISGNLDSPEGGFDAIMQVAVCGSLIGWRNVTRLLVFSTDAGFHFAGDGKLGGIVLPNDGQ
  CHLENNMYTMSHYYDYPSIAHLVQKLSENNIQTIFAVTEEFQPVYKELKNLIPKSAVGTL
  SANSSNVIQLIIDAYNSLSSEVILENGKLSEGVTISYKSYCKNGVNGTGENGRKCSNISI
  GDEVQFEISITSNKCPKKDSDSFKIRPLGFTEEVEVILQYICECECQSEGIPESPKCHEG
  NGTFECGACRCNEGRVGRHCECSTDEVNSEDMDAYCRKENSSEICSNNGECVCGQCVCRK
  RDNTNEIYSGKFCECDNFNCDRSNGLICGGNGVCKCRVCECNPNYTGSACDCSLDTSTCE
  ASNGQICNGRGICECGVCKCTDPKFQGQTCEMCQTCLGVCAEHKECVQCRAFNKGEKKDT
  CTQECSYFNITKVESRDKLPQPVQPDPVSHCKEKDVDDCWFYFTYSVNGNNEVMVHVVEN
  PECPTGPDIIPIVAGVVAGIVLIGLALLLIWKLLMIIHDRREFAKFEKEKMNAKWDTGEN
  PIYKSAVTTVVNPKYEGKMGSRTPESPLHAVQLRWGPRRRPPLLPLLLLLLPPPPRVGGF
  NLDAEAPAVLSGPPGSFFGFSVEFYRPGTDGVSVLVGAPKANTSQPGVLQGGAVYLCPWG
  ASPTQCTPIEFDSKGSRLLESSLSSSEGEEPVEYKSLQWFGATVRAHGSSILACAPLYSW
  RTEKEPLSDPVGTCYLSTDNFTRILEYAPCRSDFSWAAGQGYCQGGFSAEFTKTGRVVLG
  GPGSYFWQGQILSATQEQIAESYYPEYLINLVQGQLQTRQASSIYDDSYLGYSVAVGEFS
  GDDTEDFVAGVPKGNLTYGYVTILNGSDIRSLYNFSGEQMASYFGYAVAATDVNGDGLDD
  LLVGAPLLMDRTPDGRPQEVGRVYVYLQHPAGIEPTPTLTLTGHDEFGRFGSSLTPLGDL
  DQDGYNDVAIGAPFGGETQQGVVFVFPGGPGGLGSKPSQVLQPLWAASHTPDFFGSALRG
  GRDLDGNGYPDLIVGSFGVDKAVVYRGRPIVSASASLTIFPAMFNPEERSCSLEGNPVAC
  INLSFCLNASGKHVADSIGFTVELQLDWQKQKGGVRRALFLASRQATLTQTLLIQNGARE
  DCREMKIYLRNESEFRDKLSPIHIALNFSLDPQAPVDSHGLRPALHYQSKSRIEDKAQIL
  LDCGEDNICVPDLQLEVFGEQNHVYLGDKNALNLTFHAQNVGEGGAYEAELRVTAPPEAE
  YSGLVRHPGNFSSLSCDYFAVNQSRLLVCDLGNPMKAGASLWGGLRFTVPHLRDTKKTIQ
  FDFQILSKNLNNSQSDVVSFRLSVEAQAQVTLNGVSKPEAVLFPVSDWHPRDQPQKEEDL
  GPAVHHVYELINQGPSSISQGVLELSCPQALEGQQLLYVTRVTGLNCTTNHPINPKGLEL
  DPEGSLHHQQKREAPSRSSASSGPQILKCPEAECFRLRCELGPLHQQESQSLQLHFRVWA
  KTFLQREHQPFSLQCEAVYKALKMPYRILPRQLPQKERQVATAVQWTKAEGSYGVPLWII
  ILAILFGLLLLGLLIYILYKLGFFKRSLPYGTAMEKAQLKPPATSDA
• Function: binds to matrix macromolecules and proteinases and thereby stimulates angiogenesis. The interaction of VLA-5 with fibronectin plays an important role in regulating inflammatory cytokine production by human articular chondrocytes.
• 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)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Basigin interactions (R-HSA-210991)
  Molecules associated with elastic fibres (R-HSA-2129379)
  Integrin cell surface interactions (R-HSA-216083)
  Laminin interactions (R-HSA-3000157)
  Syndecan interactions (R-HSA-3000170)
  ECM proteoglycans (R-HSA-3000178)
  Other semaphorin interactions (R-HSA-416700)
  Localization of the PINCH-ILK-PARVIN complex to focal adhesions (R-HSA-446343)
  CHL1 interactions (R-HSA-447041)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Elastic fibre formation (R-HSA-1566948)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ATN-161	DM4T9RS	Renal cell carcinoma	2C90	Phase 2	[1]
Volociximab	DMNQG24	Non-small-cell lung cancer	2C25.Y	Phase 2	[2]
AMEP	DMFELMQ	Melanoma	2C30	Phase 1	[3]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
F-200	DMVWZN1	Ocular disease	1F00.1Z	Terminated	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Renal cancer	2C82	Kidney	2.88E-04	0.22	1.11
Lung cancer	2C82	Lung tissue	3.77E-72	-1.17	-2.04
Melanoma	2C82	Skin	4.19E-01	-0.11	-0.11

References

• [1] A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivo. Mol Cancer Ther. 2006 Sep;5(9):2271-80.
• [2] Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti-angiogenic agent. J Exp Ther Oncol. 2006;5(4):273-86.
• [3] Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma.Gene Ther.2015 Jul;22(7):578-90.
• [4] US patent application no. 8,541,413, Sustained release eye drop formulations.