Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTAU4D6)

• DTT Name: E-selectin (SELE)
• Synonyms: Leukocyte-endothelial cell adhesion molecule 2; LECAM2; Endothelial leukocyte adhesion molecule 1; ELAM1; ELAM-1; CD62E antigen; CD62E; CD62 antigen-like family member E
• Gene Name: SELE
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Acute myeloid leukaemia [ICD-11: 2A60]
  Asthma [ICD-11: CA23]
  Circulatory system disease [ICD-11: BE2Z]
  Hypertension [ICD-11: BA00-BA04]
  Atopic eczema [ICD-11: EA80]
  Chronic obstructive pulmonary disease [ICD-11: CA22]
  Psoriasis [ICD-11: EA90]
• UniProt ID: LYAM2_HUMAN
• TTD ID: T72835
• Sequence:
  MIASQFLSALTLVLLIKESGAWSYNTSTEAMTYDEASAYCQQRYTHLVAIQNKEEIEYLN
  SILSYSPSYYWIGIRKVNNVWVWVGTQKPLTEEAKNWAPGEPNNRQKDEDCVEIYIKREK
  DVGMWNDERCSKKKLALCYTAACTNTSCSGHGECVETINNYTCKCDPGFSGLKCEQIVNC
  TALESPEHGSLVCSHPLGNFSYNSSCSISCDRGYLPSSMETMQCMSSGEWSAPIPACNVV
  ECDAVTNPANGFVECFQNPGSFPWNTTCTFDCEEGFELMGAQSLQCTSSGNWDNEKPTCK
  AVTCRAVRQPQNGSVRCSHSPAGEFTFKSSCNFTCEEGFMLQGPAQVECTTQGQWTQQIP
  VCEAFQCTALSNPERGYMNCLPSASGSFRYGSSCEFSCEQGFVLKGSKRLQCGPTGEWDN
  EKPTCEAVRCDAVHQPPKGLVRCAHSPIGEFTYKSSCAFSCEEGFELHGSTQLECTSQGQ
  WTEEVPSCQVVKCSSLAVPGKINMSCSGEPVFGTVCKFACPEGWTLNGSAARTCGATGHW
  SGLLPTCEAPTESNIPLVAGLSAAGLSLLTLAPFLLWLRKCLRKAKKFVPASSCQSLESD
  GSYQKPSYIL
• Function: Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in capillary morphogenesis. Cell-surface glycoprotein having a role in immunoadhesion.
• KEGG Pathway:
  Cell adhesion molecules (CAMs) (hsa04514)
  TNF signaling pathway (hsa04668)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GMI-1070	DMJ432G	Asthma	CA23	Phase 3	[1], [2], [3]
GMI-1271	DMDTGWQ	Acute myeloid leukaemia	2A60	Phase 3	[4]
CY-1503	DML906E	Hypertension	BA00-BA04	Phase 2/3	[5]
Bimosiamose	DM0TH9A	Atopic dermatitis	EA80	Phase 2a	[6], [7], [8]
GMI-1359	DML1KSA	Breast cancer	2C60-2C65	Phase 1	[9]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SMART anti-E/P selectin	DMC49KO	Asthma	CA23	Discontinued in Phase 1	[10]
GI-270384X	DM3KN2Q	Inflammatory bowel disease	DD72	Terminated	[11]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1na	DM0A1YI	Discovery agent	N.A.	Investigative	[12]
Efomycine M	DMOKX76	Discovery agent	N.A.	Investigative	[13]
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[12]
O-Sialic Acid	DMCAR7B	Discovery agent	N.A.	Investigative	[14]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2C82	Bone marrow	6.43E-04	0.02	0.12
Atopic dermatitis	EA90	Skin	5.46E-06	0.79	1.45
Asthma	CA23	Nasal and bronchial airway	2.05E-01	0.03	0.09

References

• [1] Deal watch: Pfizer deal for selectin inhibitor highlights potential of glycomimetic drugs. Nat Rev Drug Discov. 2011 Dec 1;10(12):890.
• [2] GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice. Blood. 2010 Sep 9;116(10):1779-86.
• [3] GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice. Blood. 2010 September 9; 116(10): 1779-1786.
• [4] Clinical pipeline report, company report or official report of glycomimetics.
• [5] Adjunctive selectin blockade successfully reduces infarct size beyond thrombolysis in the electrolytic canine coronary artery model. Circulation. 1995 Aug 1;92(3):492-9.
• [6] Effects of the pan-selectin antagonist bimosiamose (TBC1269) in experimental human endotoxemia. Shock. 2008 Apr;29(4):475-82.
• [7] The pharmacokinetics of subcutaneously injected Bimosiamose disodium in healthy male volunteers. Biopharm Drug Dispos. 2007 Dec;28(9):475-84.
• [8] Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics... Pulm Pharmacol Ther. 2006;19(4):233-41.
• [9] Clinical pipeline report, company report or official report of GlycoMimetics.
• [10] HuEP5C7 as a humanized monoclonal anti-E/P-selectin neurovascular protective strategy in a blinded placebo-controlled trial of nonhuman primate stroke. Circ Res. 2002 Nov 15;91(10):907-14.
• [11] Inhibition of endothelial cell adhesion molecule expression improves colonic hyperalgaesia. Neurogastroenterol Motil. 2009 Feb;21(2):189-96.
• [12] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [13] Interfering with leukocyte rolling--a promising therapeutic approach in inflammatory skin disorders Trends Pharmacol Sci. 2003 Feb;24(2):49-52.
• [14] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.