Target Information

Target General Information

Target ID

T60526 (Former ID: TTDR00722)

Target Name

L-selectin (SELL)

Synonyms

TQ1; SELL; Lymph node homing receptor; Leukocyte-endothelial cell adhesion molecule 1; Leukocyte surface antigen Leu-8; Leukocyte adhesion molecule-1; LECAM1; LAM-1; Gp90-MEL; CD62L

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Gene Name

SELL

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Asthma [ICD-11: CA23]

Circulatory system disease [ICD-11: BE2Z]

Function

Cell surface adhesion protein. Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Promotes initial tethering and rolling of leukocytes in endothelia.

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UniProt ID

LYAM1_HUMAN

Sequence

MIFPWKCQSTQRDLWNIFKLWGWTMLCCDFLAHHGTDCWTYHYSEKPMNWQRARRFCRDN
YTDLVAIQNKAEIEYLEKTLPFSRSYYWIGIRKIGGIWTWVGTNKSLTEEAENWGDGEPN
NKKNKEDCVEIYIKRNKDAGKWNDDACHKLKAALCYTASCQPWSCSGHGECVEIINNYTC
NCDVGYYGPQCQFVIQCEPLEAPELGTMDCTHPLGNFSFSSQCAFSCSEGTNLTGIEETT
CGPFGNWSSPEPTCQVIQCEPLSAPDLGIMNCSHPLASFSFTSACTFICSEGTELIGKKK
TICESSGIWSNPSPICQKLDKSFSMIKEGDYNPLFIPVAVMVTAFSGLAFIIWLARRLKK
GKKSKRSMNDPY

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3D Structure

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AlphaFold

HIT2.0 ID

T18WSE

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

GMI-1070

Drug Info

Phase 3

Asthma

[1], [2], [3]

BAICALEIN

Drug Info

Phase 2

Influenza virus infection

[4]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 4 Inhibitor drugs

GMI-1070

Drug Info

[1], [3], [6]

BAICALEIN

Drug Info

[7]

PURPUROGALLIN

Drug Info

[7]

2,3,4-trihydroxybenzoic acid

Drug Info

[7]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1)	PF00008 ; PF00041 ; PF12661 ; PF06119 More >>	25.191 (33/131)	5.11E-05
Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3)	PF00002 ; PF00028 ; PF00008 ; PF16489 ; PF01825 ; PF00053 ; PF02210 More >>	27.193 (31/114)	2.81E-04
Cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2)	PF00002 ; PF00028 ; PF00008 ; PF16489 ; PF01825 ; PF12661 ; PF00053 ; PF02210 More >>	27.723 (28/101)	5.82E-04
Notch-3 receptor (NOTCH3)	PF12796 ; PF13857 ; PF00008 ; PF07645 ; PF12661 ; PF06816 ; PF07684 ; PF00066 More >>	31.250 (30/96)	7.83E-04


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Cell adhesion molecules	hsa04514	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy

Degree	8	Degree centrality	8.59E-04	Betweenness centrality	9.08E-04
Closeness centrality	1.98E-01	Radiality	1.34E+01	Clustering coefficient	7.14E-02
Neighborhood connectivity	9.88E+00	Topological coefficient	1.57E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Cell adhesion molecules (CAMs)

NetPath Pathway

[+] 3 NetPath Pathways

IL9 Signaling Pathway

IL2 Signaling Pathway

Leptin Signaling Pathway

Reactome

[+] 2 Reactome Pathways

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Cell surface interactions at the vascular wall

WikiPathways

[+] 3 WikiPathways

Human Complement System

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Cell surface interactions at the vascular wall

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Deal watch: Pfizer deal for selectin inhibitor highlights potential of glycomimetic drugs. Nat Rev Drug Discov. 2011 Dec 1;10(12):890.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8307).

REF 3

GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice. Blood. 2010 Sep 9;116(10):1779-86.

REF 4

ClinicalTrials.gov (NCT03830684) A Randomized, Double-blind, Placebo-controlled, Multicenter and Phase IIa Clinical Trial for the Effectiveness and Safety of Baicalein Tablets in the Treatment of Improve Other Aspects of Healthy Adult With Influenza Fever. U.S. National Institutes of Health.

REF 5

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004232)

REF 6

GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice. Blood. 2010 September 9; 116(10): 1779-1786.

REF 7

Rational design of novel, potent small molecule pan-selectin antagonists. J Med Chem. 2007 Mar 22;50(6):1101-15.

REF 8

Therapeutic applications of aptamers. Expert Opin Investig Drugs. 2008 Jan;17(1):43-60.

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