Ki: 9.36 and 13.1 nM for chymotrypsin and chymase, respectively

Chymostatin is a chymotryptase-like serine proteases inhibitor.

Serine proteases are enzymes cleaving peptide bonds, in which serine plays as the nucleophilic amino acid. Serine proteases can be classfied into two broad categories: chymotrypsin-like (trypsin-like) or subtilisin-like.

In vitro: Chymostatin was found to be a potent inhibitor of human leucocyte chymotrypsin-like protease. Its affinity to the leucocyte protease was found to be much higher than its affinity to bovine pancreatic alpha-chymotrypsin. Chymsotatin also showed a weak inhibitory effect on the activity of human leucocyte elastase. In addition, the preincubation of chymostatin with 35SO2-4-labeled cartilage before the addition of the human chymotrypsin-like protease to the tissue could also inhibit 35SO2-4 release [1].

In vivo: The effect of chymostatin on C57BL/6J-dy dystrophic mice was studied. The locomotor activity of normal mice markedly increased, attaining a plateau at 8 weeks of age. Serum levels of creatine phosphokinase were much higher in dystrophic mice when compared with normal mice, and dystrophic mice also showed a reduced muscle protein content. When 3-week-old dystrophic mice received chymostatin at 1 mg/kg, the decrease in locomotor activity could be retarded, serum enzyme levels significantly decreased, and muscle protein content also obviously increased. In addition, the survival time of chymostatin-treated dystrophic mice was prolonged [2].

Clinical trial: So far, no clinical study has been conducted.

References:
[1] Feinstein, G.?,Malemud, C.J., and Janoff, A. The inhibition of human leucocyte elastase and chymotrypsin-like protease by elastatinal and chymostatin. Biochim.Biophys.Acta. 429(3), 925-932 (1976).
[2] Komatsu K, Matsui A, Satoh S.? Beneficial effect of chymostatin on dystrophic mice. Exp Neurol. 1986 Jul;93(1):110-6.