Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE5VG0)

• DTT Name: P-selectin (SELP)
• Synonyms: SELP; PADGEM; Leukocyte-endothelial cell adhesion molecule 3; LECAM3; Granule membrane protein 140; GMP-140; CD62P
• Gene Name: SELP
• DTT Type: Successful target; [1]
• Related Disease:
  Circulatory system disease [ICD-11: BE2Z]
  Sickle-cell disorder [ICD-11: 3A51]
• UniProt ID: LYAM3_HUMAN
• TTD ID: T10965
• Sequence:
  MANCQIAILYQRFQRVVFGISQLLCFSALISELTNQKEVAAWTYHYSTKAYSWNISRKYC
  QNRYTDLVAIQNKNEIDYLNKVLPYYSSYYWIGIRKNNKTWTWVGTKKALTNEAENWADN
  EPNNKRNNEDCVEIYIKSPSAPGKWNDEHCLKKKHALCYTASCQDMSCSKQGECLETIGN
  YTCSCYPGFYGPECEYVRECGELELPQHVLMNCSHPLGNFSFNSQCSFHCTDGYQVNGPS
  KLECLASGIWTNKPPQCLAAQCPPLKIPERGNMTCLHSAKAFQHQSSCSFSCEEGFALVG
  PEVVQCTASGVWTAPAPVCKAVQCQHLEAPSEGTMDCVHPLTAFAYGSSCKFECQPGYRV
  RGLDMLRCIDSGHWSAPLPTCEAISCEPLESPVHGSMDCSPSLRAFQYDTNCSFRCAEGF
  MLRGADIVRCDNLGQWTAPAPVCQALQCQDLPVPNEARVNCSHPFGAFRYQSVCSFTCNE
  GLLLVGASVLQCLATGNWNSVPPECQAIPCTPLLSPQNGTMTCVQPLGSSSYKSTCQFIC
  DEGYSLSGPERLDCTRSGRWTDSPPMCEAIKCPELFAPEQGSLDCSDTRGEFNVGSTCHF
  SCDNGFKLEGPNNVECTTSGRWSATPPTCKGIASLPTPGLQCPALTTPGQGTMYCRHHPG
  TFGFNTTCYFGCNAGFTLIGDSTLSCRPSGQWTAVTPACRAVKCSELHVNKPIAMNCSNL
  WGNFSYGSICSFHCLEGQLLNGSAQTACQENGHWSTTVPTCQAGPLTIQEALTYFGGAVA
  STIGLIMGGTLLALLRKRFRQKDDGKCPLNPHSHLGTYGVFTNAAFDPSP
• Function: Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1.
• KEGG Pathway:
  Cell adhesion molecules (CAMs) (hsa04514)
  Malaria (hsa05144)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizanlizumab	DMAHOVJ	Vaso-occlusive crisis	BE2Y	Approved	[2]

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], [3], [4]
CY-1503	DML906E	Hypertension	BA00-BA04	Phase 2/3	[5]
BAICALEIN	DM4C7E6	Influenza virus infection	1E30-1E32	Phase 2	[6]
RPSGL-Ig	DM0BFJ5	Delayed graft function	4B24.0	Phase 2	[7], [8]
SelG1	DMTQ2K0	Vaso-occlusive crisis	BE2Y	Phase 2	[9]
PSI-697	DM75FWO	Atherosclerosis	BD40	Phase 1	[10]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CDP-850	DMWHQM3	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[11]
CY-1787	DMWY2NT	Allergy	4A80-4A85	Discontinued in Phase 1	[12]
SMART anti-E/P selectin	DMC49KO	Asthma	CA23	Discontinued in Phase 1	[13]
PURPUROGALLIN	DM63O4F	N. A.	N. A.	Terminated	[6]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1na	DM0A1YI	Discovery agent	N.A.	Investigative	[14]
2,3,4-trihydroxybenzoic acid	DMWHK35	Discovery agent	N.A.	Investigative	[6]
2-Methyl-2,4-Pentanediol	DMD45CU	Discovery agent	N.A.	Investigative	[14]
Efomycine M	DMOKX76	Discovery agent	N.A.	Investigative	[15]
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[14]
GALLICACID	DM6Y3A0	Discovery agent	N.A.	Investigative	[6]
O-Sialic Acid	DMCAR7B	Discovery agent	N.A.	Investigative	[16]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	1.72E-04	1.23	0.86

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] Crizanlizumab: First Approval. Drugs. 2020 Jan;80(1):79-84.
• [3] GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice. Blood. 2010 Sep 9;116(10):1779-86.
• [4] GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice. Blood. 2010 September 9; 116(10): 1779-1786.
• [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] Rational design of novel, potent small molecule pan-selectin antagonists. J Med Chem. 2007 Mar 22;50(6):1101-15.
• [7] rPSGL-1-Ig, a recombinant PSGL-1-Ig fusion protein, ameliorates LPS-induced acute lung injury in mice by inhibiting neutrophil migration. Cell Mol Biol (Noisy-le-grand). 2015 Feb 28;61(1):1-6.
• [8] New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
• [9] Clinical pipeline report, company report or official report of Selexys Pharmaceuticals (2011).
• [10] Effect of PSI-697, a novel P-selectin inhibitor, on platelet-monocyte aggregate formation in humans. J Am Heart Assoc. 2013 Jan 28;2(1):e006007.
• [11] WO patent application no. 2001,0276,21, Competitive inhibition elisa for antibody detection.
• [12] Administration of an antibody to E-selectin in patients with septic shock. Crit Care Med. 1996 Feb;24(2):229-33.
• [13] 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.
• [14] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [15] Interfering with leukocyte rolling--a promising therapeutic approach in inflammatory skin disorders Trends Pharmacol Sci. 2003 Feb;24(2):49-52.
• [16] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.