CEG-0598, a novel dual inhibitor of EGFR and C5aR demonstrates in vitro anticancer and antimetastatic activity in prostate cancer cells.

ABSTRACT:

Background

The EGFR is abundantly expressed in prostate cancer (PC). The anaphylatoxin C5a induces leukocyte migration via the C5a receptor (C5aR) by releasing matrix metalloproteinases (MMP) to favor metastasis in the tumor microenvironment. This work aims to selectively inhibit the EGFR and C5aR in PC cells to abort cell growth/ proliferation and metastasis.

Methods

For lead identification, high-throughput virtual screening (HTVS) of the ChemBridge library was followed by protein-ligand interaction profilers, GROMACS, and GMX-MMPBSA techniques. LNCaP and PC3 cells were used to validate in vitro efficacy.

Results

HTVS identified CEG-0598 with favorable binding affinities of - 10.2 kcal/mol and - 13.5 kcal/mol towards EGFR and C5aR respectively. Molecular dynamic simu

SUBMITTER: Dera AA 

PROVIDER: S-EPMC12064535 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature