elastase, neutrophil expressed

Target id: 2358

Nomenclature: elastase, neutrophil expressed

Family: S1: Chymotrypsin

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     elastase, neutrophil expressed has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 267 19p13.3 ELANE elastase, neutrophil expressed
Mouse - 265 10 C1 Elane elastase, neutrophil expressed
Rat - 265 7q11 Elane elastase, neutrophil expressed
Previous and Unofficial Names
medullasin | Ela2 | elastase-2 | HLE | HNE | leukocyte elastase | NE | neutrophil elastase | elastase
Database Links
Specialist databases
MEROPS S01.131 (Hs)
Other databases
BRENDA
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.21.37

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
alvelestat Hs Inhibition 8.0 pKi 4
pKi 8.0 (Ki 9.4x10-9 M) [4]
BAY-678 Hs Inhibition 7.8 pKi 6
pKi 7.8 (Ki 1.5x10-8 M) [6]
sivelestat Hs Inhibition 7.4 pIC50 1
pIC50 7.4 (IC50 4.4x10-8 M) [1]
compound 10l [PMID: 24556381] Hs Inhibition 6.2 pIC50 2
pIC50 6.2 (IC50 6.3x10-7 M) [2]
compound 10f [PMID: 24556381] Hs Inhibition 5.4 pIC50 2
pIC50 5.4 (IC50 4.22x10-6 M) [2]
compound 4g [PMID: 22595175] Hs Inhibition 5.0 pIC50 3
pIC50 5.0 (IC50 1.02x10-5 M) [3]
alpha1-proteinase inhibitor Hs Inhibition - -
Immunopharmacology Comments
Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host extracellular matrix, such as collagen-IV and elastin, hence its role in degenerative and inflammatory diseases. NE functions as a promoter of γδ T cell activation via a protease-activated receptor (PAR1)-dependent mechanism [5].
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   neutrophil (CL:0000775)
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 6 GO processes
GO:0002438 acute inflammatory response to antigenic stimulus IBA
GO:0006909 phagocytosis IBA
GO:0043312 neutrophil degranulation TAS
GO:0050728 negative regulation of inflammatory response NAS
click arrow to show/hide IEA associations
GO:0002523 leukocyte migration involved in inflammatory response IEA
GO:1903238 positive regulation of leukocyte tethering or rolling IEA
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0006909 phagocytosis IBA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0050728 negative regulation of inflammatory response NAS
click arrow to show/hide IEA associations
GO:0050778 positive regulation of immune response IEA
GO:1903238 positive regulation of leukocyte tethering or rolling IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0045079 negative regulation of chemokine biosynthetic process IDA
GO:0045415 negative regulation of interleukin-8 biosynthetic process IDA
GO:0045416 positive regulation of interleukin-8 biosynthetic process IDA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 3 GO processes
GO:0045079 negative regulation of chemokine biosynthetic process IDA
click arrow to show/hide IEA associations
GO:0002523 leukocyte migration involved in inflammatory response IEA
GO:1903238 positive regulation of leukocyte tethering or rolling IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cyclic neutropenia
Synonyms: Cyclic hematopoiesis [Disease Ontology: DOID:5339]
Disease Ontology: DOID:5339
OMIM: 162800
Orphanet: ORPHA2686
Disease:  Neutropenia, severe congenital 1, autosomal dominant
Synonyms: Autosomal dominant severe congenital neutropenia [Orphanet: ORPHA486]
Severe congenital neutropenia [Disease Ontology: DOID:0050590]
Disease Ontology: DOID:0050590
OMIM: 202700
Orphanet: ORPHA486

References

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1. Crocetti L, Giovannoni MP, Schepetkin IA, Quinn MT, Khlebnikov AI, Cilibrizzi A, Piaz VD, Graziano A, Vergelli C. (2011) Design, synthesis and evaluation of N-benzoylindazole derivatives and analogues as inhibitors of human neutrophil elastase. Bioorg. Med. Chem., 19 (15): 4460-72. [PMID:21741848]

2. Muscia GC, Hautmann S, Buldain GY, Asís SE, Gütschow M. (2014) Synthesis and evaluation of 2-(1H-indol-3-yl)-4-phenylquinolines as inhibitors of cholesterol esterase. Bioorg. Med. Chem. Lett., 24 (6): 1545-9. [PMID:24556381]

3. Santana AB, Lucas SD, Gonçalves LM, Correia HF, Cardote TA, Guedes RC, Iley J, Moreira R. (2012) N-Acyl and N-sulfonyloxazolidine-2,4-diones are pseudo-irreversible inhibitors of serine proteases. Bioorg. Med. Chem. Lett., 22 (12): 3993-7. [PMID:22595175]

4. Stevens T, Ekholm K, Gränse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk-Håkansson H, Churg A, Wright JL et al.. (2011) AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J. Pharmacol. Exp. Ther., 339 (1): 313-20. [PMID:21791628]

5. Towstyka NY, Shiromizu CM, Keitelman I, Sabbione F, Salamone GV, Geffner JR, Trevani AS, Jancic CC. (2018) Modulation of γδ T-cell activation by neutrophil elastase. Immunology, 153 (2): 225-237. [PMID:28888033]

6. von Nussbaum F, Li VM, Allerheiligen S, Anlauf S, Bärfacker L, Bechem M, Delbeck M, Fitzgerald MF, Gerisch M, Gielen-Haertwig H et al.. (2015) Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases. ChemMedChem, 10 (7): 1163-73. [PMID:26083237]

How to cite this page

S1: Chymotrypsin: elastase, neutrophil expressed. Last modified on 01/02/2018. Accessed on 18/06/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2358.