Enzymes for Research, Diagnostic and Industrial Use


Official Full Name
Chymases are a family of serine proteases found primarily in mast cells, though also present in basophil granulocytes (e.g. alpha chymase mcpt8). They show broad peptidolytic activity and are involved in a variety of functions. For example, chymases are released by mucosal mast cells upon challenge with parasites and parasite antigens promoting an inflammatory response. Chymases are also known to convert angiotensin I to angiotensin II and thus play a role in hypertension and atherosclerosis. Because of its role in inflammation it has been investigated as a target in the treatment of asthma.
mast cell protease I; skeletal muscle protease; skin chymotryptic proteinase; mast cell serine proteinase# chymase; skeletal muscle (SK) protease; chymase; EC; 97501-92-3

Product Name
EC No.
CAS No.97501-92-3
CAS No.97501-92-3
SourcePichia pastoris
Related Reading


Mast cells (MC) derived from bone marrow are considered to be the key cells involved in many non-allergic diseases and hypersensitivity. There are secretory granules in MC, when stimulated, they release various cytokines, proteoglycans, biogenic amines and proteases, such as tryptase, carboxypeptidase A, and notably chymase. The classification of MC in humans is not as complex as in rodents. According to the protease content of MC in rodents, it can be divided into MCT (expressing only MC trypsin) and MCTC (expressing both tryptase and chymase).

MC chymase (EC3.4.21.39) is a serine protease with chymotrypsin-like cleavage specificity. The crystal structure of human chymase compounded with the peptide inhibitor succinyl-Ala-Ala-Pro-Phe-chloromethylketone has been obtained. Human chymase is synthesized into an inactive prepro-enzyme and then converted into a pro-enzyme. When stored in the secretory granules of MC, chymase remains enzymatically inactive at pH 5.5; when it is released into interstitial tissues (pH 7.4), it is in the pH range of its optimal enzymatic activity (pH7-9).

This chymotrypsin-like serine protease is common in several species, namely dogs, sheep, primates, and hamsters. Humans possess a single α-chymase gene, while rats and mice have more. In addition, significant species variability has led to controversy about the possible physiological role for chymase. In recent years, the association between chymase and a variety of inflammatory diseases has been reported, especially gastrointestinal (GI) disorders. Although the research on the role of chymase in functional bowel disease is still in its infancy, preclinical studies have shown that chymase is closely related to the pathogenesis of intestinal inflammation. 

Role of chymase in disease pathogenesis Figure 1. Role of chymase in disease pathogenesis (Heuston, S.; Hyland, N.P. 2012)

Chymase inhibition: a validated target in cardiovascular and inflammatory diseases

In addition to endothelin-1, chymase also participates in the synthesis of Ang II from Ang I. At present, research into the pathophysiological role of chymase in cardiac disease has made progress, and ACE-independent Ang II synthesized by chymase is related to structural remodeling related to cardiovascular diseases. In addition to its direct enzymatic effects, chymase can also induce the activation of MMP-9 and TGF-β (the major regulators of tissue fibrosis). Therefore, chymase plays an important role in tissue fibrosis and remodeling. Thus, further suggesting the role of this protease in homeostasis regulation. A recent study by Bot et al. reported examining the contribution of chymase to atherosclerotic plaque stability in the apolipoprotein mouse model (apoE-/- mice) of human atherosclerosis.

Chymase promotes inflammation and tissue remodeling through a variety of mechanisms, including the enzymatic activation of TGF-β and MMP-9. It can be inferred that chymase inhibition may attenuate the activation of TGF-β and MMP-9, thereby directly affecting tissue inflammation and fibrosis. In fact, chymase is indeed related to the pathogenesis of inflammatory disorders, such as atopic dermatitis (AD), one of the most common chronic inflammation, and autoimmune arthritis. In addition, several genetic studies have reported the correlation between the allelic polymorphism in the chymase gene and the incidence of AD, thereby strengthening the association between chymase and AD. In addition, the results obtained after targeting chymase in pre-clinical animal models of AD are promising, and the chymase inhibitor SUN13834 is currently in phase II clinical trials for the treatment of AD.  

Therapeutic application of chymase inhibitors Figure 2. Therapeutic application of chymase inhibitors (Heuston, S.; Hyland, N.P. 2012)

Chymase inhibition: a novel therapeutic target in gastrointestinal (GI) disorders?

Regarding gastrointestinal inflammation, studies have reported an association between inflammatory bowel disease (IBD) and increased numbers of MC. However, so far, the role of chymase in IBD patients is still poorly understood. It is worth noting that the chymase in IBD, the number of chymase-containing MC between ulcerative colitis (UC) and Crohn's disease (CD), and between active and inactive phases of inflammation have undergone divergent changes. In particular, Andoh et al. noted that the chymase immunopositive MC in the colonic mucosa of patients with active CD increased significantly not only in the lamina propria, but also in the submucosa, propria muscularis and surrounding fatty tissue.

Unlike IBD, irritable bowel syndrome (IBS) is a common sensory and motility disorder, and its pathophysiology is not fully understood. A sensitive and specific assay for the determination of serum chymase activity has been developed. Raymond et al. used the α2-macroglobulin binding properties of chymase to evaluate the chymase activity in the serum of subjects with mastocytosis. Recent evidence suggests the use of secretory leucocyte protease inhibitor (SLPI) lysate as a new biomarker of chymase activity. Chymase may play a role in the barrier breakdown associated with IBS, and there is evidence that the release of tryptase is regulated by chymase. Therefore, chymotrypsin and tryptase may jointly cause IBS-related symptoms. Although a chymostatin-sensitive tryptase-release pathway has been identified in MC isolated from the gastrointestinal tract, to date, this pathway has not been investigated in IBS.   


  1. Heuston, S.; Hyland, N.P. Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders? British Journal of Pharmacology. 2012, 167: 732-740.

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