Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTCT6F7)

• DTT Name: Intercellular adhesion molecule ICAM-1 (ICAM1)
• Synonyms: Major group rhinovirus receptor; Intercellular adhesion molecule 1; ICAM-1; CD54
• Gene Name: ICAM1
• DTT Type: Successful target; [1]
• BioChemical Class: Immunoglobulin
• UniProt ID: ICAM1_HUMAN
• TTD ID: T26203
• 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
lifitegrast	DM4WVC5	Dry eye disease	9E1Z	Approved	[1]

4 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]
APC-8015F	DM3VP19	Prostate cancer	2C82.0	Phase 2	[3]
BI-505	DMSZQHX	Multiple myeloma	2A83	Phase 2	[4]
AIC100	DMSPBOW	Thyroid cancer	2D10	Phase 1	[5]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-252444.0	DMDTA36	Inflammation	1A00-CA43.1	Terminated	[6]
GI-270384X	DM3KN2Q	Inflammatory bowel disease	DD72	Terminated	[7]
MOR-102	DMRCH1M	Psoriasis vulgaris	EA90	Terminated	[8]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS-1939	DMGN4OQ	Discovery agent	N.A.	Investigative	[9]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	5.21E-01	0.38	0.32
Multiple myeloma	2C82	Bone marrow	4.00E-01	0.04	0.13
Psoriasis	EA90	Skin	9.18E-01	0.04	0.07

References

• [1] Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye. ACS Med Chem Lett. 2012 Jan 31;3(3):203-6.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] National Cancer Institute Drug Dictionary (drug id 561410).
• [4] A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer Cell. 2013 Apr 15;23(4):502-15.
• [5] Clinical pipeline report, company report or official report of AffyImmune Therapeutics.
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012566)
• [7] Inhibition of endothelial cell adhesion molecule expression improves colonic hyperalgaesia. Neurogastroenterol Motil. 2009 Feb;21(2):189-96.
• [8] Efficacy of the fully human monoclonal antibody MOR102 (#5) against intercellular adhesion molecule 1 in the psoriasis-severe combined immunodeficient mouse model. Br J Dermatol. 2005 Oct;153(4):758-66.
• [9] Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms. J Biol Chem. 1991 Sep 25;266(27):18162-71.