chymase 1

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 2340

Nomenclature: chymase 1

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	247	14q12	CMA1	chymase 1
Mouse	-	247	14 28.19 cM	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
Alphafold	P23946 (Hs), P21844 (Mm), P50339 (Rn)
BRENDA	3.4.21.39
ChEMBL Target	CHEMBL4068 (Hs), CHEMBL3168 (Rn)
Ensembl Gene	ENSG00000092009 (Hs), ENSMUSG00000022225 (Mm), ENSRNOG00000020563 (Rn)
Entrez Gene	1215 (Hs), 17228 (Mm), 25627 (Rn)
Human Protein Atlas	ENSG00000092009 (Hs)
KEGG Enzyme	3.4.21.39
KEGG Gene	hsa:1215 (Hs), mmu:17228 (Mm), rno:25627 (Rn)
OMIM	118938 (Hs)
Pharos	P23946 (Hs)
RefSeq Nucleotide	NM_001836 (Hs), NM_010780 (Mm), NM_013092 (Rn)
RefSeq Protein	NP_001827 (Hs), NP_034910 (Mm), NP_037224 (Rn)
SynPHARM	84824 (in complex with compound 7f [PMID: 29191554]) 78440 (in complex with JNJ-10311795)
UniProtKB	P23946 (Hs), P21844 (Mm), P50339 (Rn)
Wikipedia	CMA1 (Hs)

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

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Inhibitors

Key to terms and symbols

View all chemical structures

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Ligand		Sp.	Action	Value	Parameter	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]).

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

Immuno Process:

Immune regulation

Immuno Process:

Cytokine production & signalling

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]