Glycosyl hydrolase family 18 chitinase (GH18) (GH18)

Glycosyl hydrolase family 18 (GH18) chitinases are a group of proteins including enzymatically active chitinases like chitotriosidase-1 (CHIT1) and acidic mammalian chitinase (AMCase), as well as chitinase-like proteins (CLPs) such as YKL-40 (CHI3L1) (Bussink et al., 2007, PMID: 17210962). While humans do not synthesize chitin, these enzymes are part of the innate immune system, evolved to degrade chitinous pathogens like fungi and helminths (Kzhyshkowska et al., 2016, PMID: 27833629). In disease states, GH18 members are significantly upregulated and serve as mediators of Th2-driven inflammation, tissue remodeling, and fibrosis in conditions such as asthma, sarcoidosis, and idiopathic pulmonary fibrosis (IPF) (Sutherland et al., 2014, PMID: 24713986). Therapeutic targeting of this family involves small-molecule inhibitors like OATD-01, which dual-targets CHIT1 and AMCase to reduce fibrotic progression (Molecure, 2023). These proteins also serve as important biomarkers; for instance, CHIT1 activity is a diagnostic marker for Gaucher disease, and YKL-40 levels correlate with poor prognosis in various cancers and inflammatory disorders.

Other names

Chitinase family 18Mammalian chitinasesChitinase-like proteinsCLPs18-glycosyl hydrolase

Inhibition of the catalytic activity of active chitinases (CHIT1 and AMCase) by binding to the active site, or blocking the chitin-binding domain of chitinase-like proteins to modulate inflammatory signaling (Bussink et al., 2007, PMID: 17210962).