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]
• 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

6 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]
GMI-1271	DMDTGWQ	Acute myeloid leukaemia	2A60	Phase 3	[2]
CY-1503	DML906E	Hypertension	BA00-BA04	Phase 2/3	[3]
Bimosiamose	DM0TH9A	Atopic dermatitis	EA80	Phase 2a	[4]
GMI-1359	DML1KSA	Breast cancer	2C60-2C65	Phase 1	[5]
PF-07209326	DM7YRAL	Sickle-cell disorder	3A51	Phase 1	[6]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GI-270384X	DM3KN2Q	Inflammatory bowel disease	DD72	Terminated	[7]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1na	DM0A1YI	Discovery agent	N.A.	Investigative	[8]
Efomycine M	DMOKX76	Discovery agent	N.A.	Investigative	[9]
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[8]
O-Sialic Acid	DMCAR7B	Discovery agent	N.A.	Investigative	[10]

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] Clinical pipeline report, company report or official report of glycomimetics.
• [3] Adjunctive selectin blockade successfully reduces infarct size beyond thrombolysis in the electrolytic canine coronary artery model. Circulation. 1995 Aug 1;92(3):492-9.
• [4] Effects of the pan-selectin antagonist bimosiamose (TBC1269) in experimental human endotoxemia. Shock. 2008 Apr;29(4):475-82.
• [5] Clinical pipeline report, company report or official report of GlycoMimetics.
• [6] ClinicalTrials.gov (NCT04255875) A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED EVALUATION OF SINGLE DOSES OF PF-07209326 IN HEALTHY PARTICIPANTS (SAFETY, TOLERABILITY, AND PHARMACOKINETICS [PK]) FOLLOWED BY AN OPEN LABEL, REPEAT DOSE EVALUATION IN SICKLE CELL DISEASE PARTICIPANTS (SAFETY, TOLERABILITY, PK AND EFFICACY). U.S.National Institutes of Health.
• [7] Inhibition of endothelial cell adhesion molecule expression improves colonic hyperalgaesia. Neurogastroenterol Motil. 2009 Feb;21(2):189-96.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [9] Interfering with leukocyte rolling--a promising therapeutic approach in inflammatory skin disorders Trends Pharmacol Sci. 2003 Feb;24(2):49-52.
• [10] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.