Human chitinases and chitinase-like proteins as emerging drug targets – a medicinal chemistry perspective

Abstract

Human chitinases and chitinase-like proteins (CLPs) provide the immune system with the ability to recognize or process chitin originating from chitinous pathogens. In addition to their role in host defense, most members of this protein family have evolved pleiotropic cellular effector functions broadly related to immune homeostasis, cell proliferation, and tissue remodeling. This wide-ranging ability to modulate crucial cellular processes proceeds via the activation of cellular signal transduction cascades and appears to be fully independent of chitin recognition. Dysregulation of chitinase/CLP functions has been linked to a plethora of inflammatory diseases, such as allergic airway diseases and asthma, fibrosis, as well as cancer. This fact predetermines certain members of this protein family as prime targets for pharmacological intervention. Here, we provide an extensive review of medicinal chemistry efforts targeting the most widely studied members of the human chitinase/CLP family, namely acidic mammalian chitinase (AMCase), chitotriosidase (CHIT1), and chitinase-3-like protein 1 (CHI3L1/YKL-40).