Structure-based design of orthosteric and allosteric CCR2 inhibitors for potential IPF therapy.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease with an extremely poor prognosis. Our previous studies revealed that CCR2 (C-C chemokine receptor type 2) expression is significantly upregulated in bleomycin-induced pulmonary fibrosis in mice. Moreover, bioinformatics analysis indicated that higher CCR2 expression is associated with poorer prognosis in patients. Therefore, we proposed a novel dual-target intervention strategy focused on the orthosteric and allosteric binding sites of the CCR2 receptor. By integrating structure-based pharmacophore modeling, 3D-QSAR, common feature pharmacophore modeling, and large-scale virtual screening (covering 152 406 molecules), we successfully identified two candidate small molecules, compound 17 and compound 67, that exhibit high si

SUBMITTER: Yan G 

PROVIDER: S-EPMC12570389 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature