CCN family of cysteine-rich proteins (CCN family)

The CCN family of cysteine-rich proteins (comprising CCN1/CYR61, CCN2/CTGF, CCN3/NOV, and others) consists of matricellular proteins that play essential roles in regulating cell adhesion, migration, proliferation, and angiogenesis. These proteins are characterized by a conserved four-domain structure with a high concentration of cysteine residues, which are critical for maintaining structural integrity and mediating interactions with cell surface receptors such as integrins and heparan sulfate proteoglycans. In a broader therapeutic context, the term "cysteine-rich cellular proteins" is also used to describe the general pool of intracellular proteins with reactive thiol groups (including metallothioneins and zinc-finger proteins) that are targeted by electrophilic drugs and metabolites. Dysregulation of these proteins is frequently observed in pathologies such as cancer, chronic fibrosis, and cardiovascular diseases, making them significant targets for drug development. For example, pamrevlumab is a monoclonal antibody targeting CCN2 (CTGF) that has been investigated in clinical trials for idiopathic pulmonary fibrosis and pancreatic cancer, while small molecules like naphthoquinones exert their effects through the alkylation of these cysteine-rich targets.

Other names

CCN family of cysteine-rich proteinsCyr61/CTGF/Nov familyCysteine-rich protein (CRP) familyCysteine-rich intestinal protein (CRIP) familyCellular thiol-rich proteinsCysteine-rich angiogenic inducer 61 (CYR61)Connective tissue growth factor (CTGF)

Monoclonal antibody-mediated inhibition of matricellular signaling; Alkylation of reactive cysteine residues; Induction of oxidative stress via redox cycling