Connective Tissue Growth Factor: Regulation, Diseases, and Drug Discovery

Abstract

In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.

Keywords: CTGF-related diseases; CTGF/CCN2; drug discovery; regulation mechanism; therapeutic target.

Figure 1

Three-dimensional structure of the CTGF protein. The human CTGF structural PDB file was obtained from the AlphaFold Protein Structure Database (https://alphafold.com/, accessed on 7 April 2024).

Figure 2

Diagram of the interaction network between CTGF’s domains and different molecules, signaling pathways, and diseases. Abbreviations: BMP, bone morphogenetic proteins; CT, cysteine knot-containing domain; EGF, epidermal growth factor; ER, estrogen receptors; FAK, focal adhesion kinase; FGFs, fibroblast growth factors; HSPG, heparan sulfate proteoglycan; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; LATS, long-acting thyroid stimulator; LRP, low-density lipoprotein receptor-related protein; MRTF-A, myocardin-related transcription factor A; RhoA, ras homolog family member A; SLIT2, slit guidance ligand 2; TGF-β, transforming growth factor-β; TSP-1, thrombospondin type-1 repeat; VWC, von Willebrand factor type C repeat; Wif, Wnt inhibitory factor; YAP, Yes-associated protein.

Figure 3

Structures of marketed compounds for CTGF-targeted and -inhibitory therapy. The chemical structures were obtained from the Drugbank online database (https://go.drugbank.com/, accessed on 7 April 2024).