Target Information
Target General Information | Top | |||||
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Target ID |
T21865
(Former ID: TTDR01112)
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Target Name |
P-selectin glycoprotein ligand 1 (SELPLG)
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Synonyms |
Selectin P ligand; SPSGL-1; SELPLG; PSGL-1; P-selectin glycoprotein ligand-1; CD162 antigen
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Gene Name |
SELPLG
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 5 Target-related Diseases | + | ||||
1 | Allergic/hypersensitivity disorder [ICD-11: 4A80-4A8Z] | |||||
2 | Asthma [ICD-11: CA23] | |||||
3 | Chronic obstructive pulmonary disease [ICD-11: CA22] | |||||
4 | Myocardial infarction [ICD-11: BA41-BA43] | |||||
5 | Psoriatic arthritis [ICD-11: FA21] | |||||
Function |
A SLe(x)-type proteoglycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial steps in inflammation. Critical for the initial leukocyte capture.
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UniProt ID | ||||||
Sequence |
MPLQLLLLLILLGPGNSLQLWDTWADEAEKALGPLLARDRRQATEYEYLDYDFLPETEPP
EMLRNSTDTTPLTGPGTPESTTVEPAARRSTGLDAGGAVTELTTELANMGNLSTDSAAME IQTTQPAATEAQTTQPVPTEAQTTPLAATEAQTTRLTATEAQTTPLAATEAQTTPPAATE AQTTQPTGLEAQTTAPAAMEAQTTAPAAMEAQTTPPAAMEAQTTQTTAMEAQTTAPEATE AQTTQPTATEAQTTPLAAMEALSTEPSATEALSMEPTTKRGLFIPFSVSSVTHKGIPMAA SNLSVNYPVGAPDHISVKQCLLAILILALVATIFFVCTVVLAVRLSRKGHMYPVRNYSPT EMVCISSLLPDGGEGPSATANGGLSKAKSPGLTPEPREDREGDDLTLHSFLP Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
1 | AbGn-168 | Drug Info | Phase 2 | Allergy | [2] | |
2 | Neihulizumab | Drug Info | Phase 2 | Psoriatic arthritis | [3] | |
3 | RO-4905417 | Drug Info | Phase 2 | Acute coronary syndrome | [4] | |
4 | SelK2 | Drug Info | Phase 2 | Asthma | [5] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | Neihulizumab | Drug Info | [3] | |||
2 | SelK2 | Drug Info | [7] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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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
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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.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Cell adhesion molecules | hsa04514 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
Neutrophil extracellular trap formation | hsa04613 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy |
Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 1.86E-05 |
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Closeness centrality | 1.86E-01 | Radiality | 1.31E+01 | Clustering coefficient | 3.00E-01 |
Neighborhood connectivity | 1.60E+01 | Topological coefficient | 2.74E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
1 | Cell adhesion molecules (CAMs) | |||||
2 | Staphylococcus aureus infection | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | amb2 Integrin signaling | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Cell surface interactions at the vascular wall | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Human Complement System | |||||
2 | Cell surface interactions at the vascular wall |
References | Top | |||||
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REF 1 | Clinical pipeline report, company report or official report of Avarx. | |||||
REF 2 | ClinicalTrials.gov (NCT01855880) Phase IIa Study of Multiple Doses of AbGn-168H by iv Infusion in Moderate to Severe Chronic Plaque Psoriasis Patients. U.S. National Institutes of Health. | |||||
REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 4 | ClinicalTrials.gov (NCT01245634) A Study of RO4905417 in Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery. U.S. National Institutes of Health. | |||||
REF 5 | ClinicalTrials.gov (NCT04540042) A Two Part, Randomised, Double-blind, Placebo-controlled, Phase 2 Parallel Group Study to Evaluate the Safety and Efficacy of Intravenously-Administered SelK2 on Airway Responses Following Allergen Challenge in Subjects With Asthma (Part 1) and to Evaluate the Safety and Efficacy of Intravenously-Administered SelK2 in Subjects With Chronic Obstructive Pulmonary Disease (Part 2). U.S.National Institutes of Health. | |||||
REF 6 | WO patent application no. 2013,0144,05, Methods. | |||||
REF 7 | Clinical pipeline report, company report or official report of Tetherex Pharmaceuticals |
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