Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTA1L39)

• DTT Name: ICAM1 messenger RNA (ICAM1 mRNA)
• Synonyms: Major group rhinovirus receptor (mRNA); Intercellular adhesion molecule 1 (mRNA); ICAM-1 (mRNA); CD54 (mRNA)
• Gene Name: ICAM1
• DTT Type: Successful target; [1]
• BioChemical Class: mRNA target
• UniProt ID: ICAM1_HUMAN
• TTD ID: T57011
• Sequence:
  MAPSSPRPALPALLVLLGALFPGPGNAQTSVSPSKVILPRGGSVLVTCSTSCDQPKLLGI
  ETPLPKKELLLPGNNRKVYELSNVQEDSQPMCYSNCPDGQSTAKTFLTVYWTPERVELAP
  LPSWQPVGKNLTLRCQVEGGAPRANLTVVLLRGEKELKREPAVGEPAEVTTTVLVRRDHH
  GANFSCRTELDLRPQGLELFENTSAPYQLQTFVLPATPPQLVSPRVLEVDTQGTVVCSLD
  GLFPVSEAQVHLALGDQRLNPTVTYGNDSFSAKASVSVTAEDEGTQRLTCAVILGNQSQE
  TLQTVTIYSFPAPNVILTKPEVSEGTEVTVKCEAHPRAKVTLNGVPAQPLGPRAQLLLKA
  TPEDNGRSFSCSATLEVAGQLIHKNQTRELRVLYGPRLDERDCPGNWTWPENSQQTPMCQ
  AWGNPLPELKCLKDGTFPLPIGESVTVTRDLEGTYLCRARSTQGEVTRKVTVNVLSPRYE
  IVIITVVAAAVIMGTAGLSTYLYNRQRKIKKYRLQQAQKGTPMKPNTQATPP
• Function: During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2).
• KEGG Pathway:
  NF-kappa B signaling pathway (hsa04064)
  Cell adhesion molecules (CAMs) (hsa04514)
  Natural killer cell mediated cytotoxicity (hsa04650)
  TNF signaling pathway (hsa04668)
  Leukocyte transendothelial migration (hsa04670)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
  Staphylococcus aureus infection (hsa05150)
  Influenza A (hsa05164)
  HTLV-I infection (hsa05166)
  Epstein-Barr virus infection (hsa05169)
  Rheumatoid arthritis (hsa05323)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Integrin cell surface interactions (R-HSA-216083)
  Interferon gamma signaling (R-HSA-877300)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 1570	DMJ9G23	Lleum inflammation	1A40.0	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alicaforsen	DMQ509J	Lleum inflammation	1A40.0	Phase 3	[2]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INXC-ICAM1	DMODQW0	Transplant rejection	NE84	Terminated	[3]

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-286982	DM98VFW	Discovery agent	N.A.	Investigative	[4]
Dehydropipernonaline	DMIOA9M	Discovery agent	N.A.	Investigative	[5]
ISIS 11158	DMX1OI8	Discovery agent	N.A.	Investigative	[6]
ISIS 11159	DM9V6FW	Discovery agent	N.A.	Investigative	[6]
ISIS 11665	DMYWINR	Discovery agent	N.A.	Investigative	[6]
ISIS 1931	DMBMQNI	Discovery agent	N.A.	Investigative	[1]
ISIS 2974	DM7K19L	Discovery agent	N.A.	Investigative	[1]
ISIS 3067	DMC9OL7	Discovery agent	N.A.	Investigative	[6]
ISIS 3224	DMAFEYG	Discovery agent	N.A.	Investigative	[6]
Pellitorin	DMYIWBD	Discovery agent	N.A.	Investigative	[5]
PIPERNONALINE	DMB3NZA	Discovery agent	N.A.	Investigative	[5]
PIPERROLEIN B	DMRVHWZ	Discovery agent	N.A.	Investigative	[5]

References

• [1] US patent application no. 6,300,491, Oligonucleotide inhibition of cell adhesion.
• [2] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009).
• [3] ISIS 2302. INXC ICAM1, Oligo-TCS. Drugs R D. 1999 Jan;1(1):85-6.
• [4] 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.
• [5] Alkamides from the fruits of Piper longum and Piper nigrum displaying potent cell adhesion inhibition. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4544-6.
• [6] US patent application no. 5,789,573, Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2.