chymase 1

Target id: 2340

Nomenclature: chymase 1

Family: S1: Chymotrypsin

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     chymase 1 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 247 14q12 CMA1 chymase 1
Mouse - 260 14 C3 Cma1 chymase 1, mast cell
Rat - 247 15p13 Cma1 chymase 1
Previous and Unofficial Names
alpha-chymase | chymase 1, mast cell | mast cell protease 3 | mast cell protease 5 | mast cell protease I | mast cell protease III | MCP3P | Mcp5
Database Links
Specialist databases
MEROPS S01.140 (Hs)
Other databases
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Human chymase in complex with 7-oxo-3-(phenoxyimino)-1,4-diazepane derivative (compound 7f).
PDB Id:  5YJM
Ligand:  compound 7f [PMID: 29191554]
Resolution:  1.9Å
Species:  Human
References:  1
Enzyme Reaction
EC Number: 3.4.21.39

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
NK3201 Hs Inhibition 8.6 pIC50 8
pIC50 8.6 (IC50 2.5x10-9 M) [8]
JNJ-10311795 Hs Inhibition 8.3 pIC50 2
pIC50 8.3 (IC50 4.5x10-9 M) [2]
TY-51469 Hs Inhibition 8.1 pIC50 5,7
pIC50 8.1 (IC50 7x10-9 M) [5,7]
compound 7f [PMID: 29191554] Hs Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 8.9x10-9 M) [1]
Immunopharmacology Comments
Chymase is a chymotrypsin-like serine protease that is expressed by mast cells. Amongst its activities, chymase is involved in the conversion of angiotensin (AT) I to ATII, its protease activity cleaves latent TGFβ1 and IL-1β in the cellular environment to generate the active cytokines, and it can further stimulate mast cell degranulation in a self-amplification loop. The potential of chymase as a drug target for inflammatory and gastrointestinal disorders is reviewed by Heuston and Hyland (2012) [3]. Chymase inhibitors are being investigated for anti-inflammatory potential [4,7] (and cardiovascular disease [10]).
Cell Type Associations
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  Chymase is present in mast cell secretory granules.
References:  6,9
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0050727 regulation of inflammatory response IC
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050727 regulation of inflammatory response IC
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0050720 interleukin-1 beta biosynthetic process IDA

References

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1. Futamura-Takahashi J, Tanaka T, Sugawara H, Iwashita S, Imajo S, Oyama Y, Muto T. (2018) Structure-based design, synthesis, and binding mode analysis of novel and potent chymase inhibitors. Bioorg. Med. Chem. Lett., 28 (2): 188-192. [PMID:29191554]

2. Greco MN, Hawkins MJ, Powell ET, Almond Jr HR, de Garavilla L, Hall J, Minor LK, Wang Y, Corcoran TW, Di Cera E et al.. (2007) Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase. J. Med. Chem., 50 (8): 1727-30. [PMID:17361995]

3. Heuston S, Hyland NP. (2012) Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders?. Br. J. Pharmacol., 167 (4): 732-40. [PMID:22646261]

4. Liu WX, Wang Y, Sang LX, Zhang S, Wang T, Zhou F, Gu SZ. (2016) Chymase inhibitor TY-51469 in therapy of inflammatory bowel disease. World J. Gastroenterol., 22 (5): 1826-33. [PMID:26855541]

5. Palaniyandi SS, Nagai Y, Watanabe K, Ma M, Veeraveedu PT, Prakash P, Kamal FA, Abe Y, Yamaguchi K, Tachikawa H et al.. (2007) Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Exp. Biol. Med. (Maywood), 232 (9): 1213-21. [PMID:17895529]

6. Schwartz LB, Austen KF. (1980) Enzymes of the mast cell granule. J. Invest. Dermatol., 74 (5): 349-53. [PMID:6771334]

7. Takato H, Yasui M, Ichikawa Y, Waseda Y, Inuzuka K, Nishizawa Y, Tagami A, Fujimura M, Nakao S. (2011) The specific chymase inhibitor TY-51469 suppresses the accumulation of neutrophils in the lung and reduces silica-induced pulmonary fibrosis in mice. Exp. Lung Res., 37 (2): 101-8. [PMID:21128860]

8. Tsunemi K, Takai S, Nishimoto M, Jin D, Sakaguchi M, Muramatsu M, Yuda A, Sasaki S, Miyazaki M. (2004) A specific chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2-heptyl]acetamide (NK3201), suppresses development of abdominal aortic aneurysm in hamsters. J. Pharmacol. Exp. Ther., 309 (3): 879-83. [PMID:14960660]

9. Welle M. (1997) Development, significance, and heterogeneity of mast cells with particular regard to the mast cell-specific proteases chymase and tryptase. J. Leukoc. Biol., 61 (3): 233-45. [PMID:9060446]

10. Yahiro E, Miura S, Imaizumi S, Uehara Y, Saku K. (2013) Chymase inhibitors. Curr. Pharm. Des., 19 (17): 3065-71. [PMID:23176221]

How to cite this page

S1: Chymotrypsin: chymase 1. Last modified on 15/02/2018. Accessed on 18/07/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2340.