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elastase, neutrophil expressed

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2358

Nomenclature: elastase, neutrophil expressed

Family: S1: Chymotrypsin

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 267 19p13.3 ELANE elastase, neutrophil expressed
Mouse - 265 10 39.72 cM Elane elastase, neutrophil expressed
Rat - 265 7q11 Elane elastase, neutrophil expressed
Previous and Unofficial Names Click here for help
medullasin | HNE | Ela2 | elastase-2 | HLE | leukocyte elastase | NE | neutrophil elastase | elastase
Database Links Click here for help
Specialist databases
MEROPS S01.131 (Hs)
Other databases
Alphafold P08246 (Hs), Q3UP87 (Mm)
BRENDA 3.4.21.37
ChEMBL Target CHEMBL248 (Hs), CHEMBL5156 (Mm)
DrugBank Target P08246 (Hs)
Ensembl Gene ENSG00000197561 (Hs), ENSMUSG00000020125 (Mm), ENSRNOG00000033685 (Rn)
Entrez Gene 1991 (Hs), 50701 (Mm), 299606 (Rn)
Human Protein Atlas ENSG00000197561 (Hs)
KEGG Enzyme 3.4.21.37
KEGG Gene hsa:1991 (Hs), mmu:50701 (Mm), rno:299606 (Rn)
OMIM 130130 (Hs)
Orphanet ORPHA121511 (Hs)
Pharos P08246 (Hs)
RefSeq Nucleotide NM_001972 (Hs), NM_015779 (Mm), NM_001106767 (Rn)
RefSeq Protein NP_001963 (Hs), NP_056594 (Mm), NP_001100237 (Rn)
UniProtKB P08246 (Hs), Q3UP87 (Mm)
Wikipedia ELANE (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.21.37

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
alvelestat Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 8.0 pKi 4
⤷ pKi 8.0 (Ki 9.4x10-9 M) [4]
BAY-678 Small molecule or natural product Primary target of this compound Hs Inhibition 7.8 pKi 7
⤷ pKi 7.8 (Ki 1.5x10-8 M) [7]
sivelestat Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.4 pIC50 1
⤷ pIC50 7.4 (IC50 4.4x10-8 M) [1]
compound 10l [PMID: 24556381] Small molecule or natural product Hs Inhibition 6.2 pIC50 2
⤷ pIC50 6.2 (IC50 6.3x10-7 M) [2]
compound 10f [PMID: 24556381] Small molecule or natural product Hs Inhibition 5.4 pIC50 2
⤷ pIC50 5.4 (IC50 4.22x10-6 M) [2]
compound 4g [PMID: 22595175] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.0 pIC50 3
⤷ pIC50 5.0 (IC50 1.02x10-5 M) [3]
alpha1-proteinase inhibitor Peptide Approved drug Primary target of this compound Hs Inhibition - -
⤷
poststatin Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 6
⤷ [6]
Description: IC50 is 110 μg/ml in vitro.
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
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
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. Tsuda M, Muraoka Y, Nagai M, Aoyagi T, Takeuchi T. (1996) Poststatin, a new inhibitor of prolyl endopeptidase. V. Endopeptidase inhibitory activity of poststatin analogues. J Antibiot, 49 (9): 890-9. [PMID:8931723]

7. 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 07/10/2020. Accessed on 15/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2358.