Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTSJ542)

• DTT Name: Integrin alpha-2 (ITGA2)
• Synonyms: VLA-2 subunit alpha; VLA-2 alphachain; VLA-2; Platelet membrane glycoprotein Ia; Platelet glycoprotein Ia/IIa; Glycoprotein Ia-IIa; GPIa/IIa; GPIa; Collagen receptor; CD49b; CD49 antigen-like family member B; Adhesive platelet receptor alpha1 beta2
• Gene Name: ITGA2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Integrin
• UniProt ID: ITA2_HUMAN
• TTD ID: T55293
• Sequence:
  MGPERTGAAPLPLLLVLALSQGILNCCLAYNVGLPEAKIFSGPSSEQFGYAVQQFINPKG
  NWLLVGSPWSGFPENRMGDVYKCPVDLSTATCEKLNLQTSTSIPNVTEMKTNMSLGLILT
  RNMGTGGFLTCGPLWAQQCGNQYYTTGVCSDISPDFQLSASFSPATQPCPSLIDVVVVCD
  ESNSIYPWDAVKNFLEKFVQGLDIGPTKTQVGLIQYANNPRVVFNLNTYKTKEEMIVATS
  QTSQYGGDLTNTFGAIQYARKYAYSAASGGRRSATKVMVVVTDGESHDGSMLKAVIDQCN
  HDNILRFGIAVLGYLNRNALDTKNLIKEIKAIASIPTERYFFNVSDEAALLEKAGTLGEQ
  IFSIEGTVQGGDNFQMEMSQVGFSADYSSQNDILMLGAVGAFGWSGTIVQKTSHGHLIFP
  KQAFDQILQDRNHSSYLGYSVAAISTGESTHFVAGAPRANYTGQIVLYSVNENGNITVIQ
  AHRGDQIGSYFGSVLCSVDVDKDTITDVLLVGAPMYMSDLKKEEGRVYLFTIKKGILGQH
  QFLEGPEGIENTRFGSAIAALSDINMDGFNDVIVGSPLENQNSGAVYIYNGHQGTIRTKY
  SQKILGSDGAFRSHLQYFGRSLDGYGDLNGDSITDVSIGAFGQVVQLWSQSIADVAIEAS
  FTPEKITLVNKNAQIILKLCFSAKFRPTKQNNQVAIVYNITLDADGFSSRVTSRGLFKEN
  NERCLQKNMVVNQAQSCPEHIIYIQEPSDVVNSLDLRVDISLENPGTSPALEAYSETAKV
  FSIPFHKDCGEDGLCISDLVLDVRQIPAAQEQPFIVSNQNKRLTFSVTLKNKRESAYNTG
  IVVDFSENLFFASFSLPVDGTEVTCQVAASQKSVACDVGYPALKREQQVTFTINFDFNLQ
  NLQNQASLSFQALSESQEENKADNLVNLKIPLLYDAEIHLTRSTNINFYEISSDGNVPSI
  VHSFEDVGPKFIFSLKVTTGSVPVSMATVIIHIPQYTKEKNPLMYLTGVQTDKAGDISCN
  ADINPLKIGQTSSSVSFKSENFRHTKELNCRTASCSNVTCWLKDVHMKGEYFVNVTTRIW
  NGTFASSTFQTVQLTAAAEINTYNPEIYVIEDNTVTIPLMIMKPDEKAEVPTGVIIGSII
  AGILLLLALVAILWKLGFFKRKYEKMTKNPDEIDETTELSS
• Function: It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix. Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin.
• KEGG Pathway:
  Phagosome (hsa04145)
  PI3K-Akt signaling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Platelet activation (hsa04611)
  Hematopoietic cell lineage (hsa04640)
  Regulation of actin cytoskeleton (hsa04810)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Small cell lung cancer (hsa05222)
  Hypertrophic cardiomyopathy (HCM) (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Laminin interactions (R-HSA-3000157)
  Syndecan interactions (R-HSA-3000170)
  ECM proteoglycans (R-HSA-3000178)
  CHL1 interactions (R-HSA-447041)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  Integrin cell surface interactions (R-HSA-216083)

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
E7820	DMZRXTL	Colorectal cancer	2B91.Z	Phase 2	[1]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-(3-(benzamido)-5-nitrobenzamido)propanoic acid	DMY4VX2	Discovery agent	N.A.	Investigative	[2]
3-(3-(carbamoyl)benzamido)-3-phenylpropanoic acid	DM2K51S	Discovery agent	N.A.	Investigative	[2]
3-(3-(carbamoyl)benzamido)propanoic acid	DM31JAZ	Discovery agent	N.A.	Investigative	[2]
MAGGIEMYCIN	DMSQL19	Discovery agent	N.A.	Investigative	[3]

References

• [1] Phase I study of E7820, an oral inhibitor of integrin alpha-2 expression with antiangiogenic properties, in patients with advanced malignancies. Clin Cancer Res. 2011 Jan 1;17(1):193-200.
• [2] Derivatives of 7-amino-1,2,3,4-tetrahydroisoquinoline and isophthalic acids as novel fibrinogen receptor antagonists. Bioorg Med Chem Lett. 2006 Oct 15;16(20):5294-7.
• [3] Small molecule designed to target metal binding site in the alpha2I domain inhibits integrin function. J Med Chem. 2007 May 31;50(11):2742-6.