Combining AlphaFold with Focused Virtual Library Design in the Development of Novel CCR2 and CCR5 Antagonists.

ABSTRACT: CC chemokine receptor (CCR) 2 and 5 are G protein-coupled receptors that play a crucial role in immunohomeostasis. Accordingly, overactivation of their signaling pathways is involved in various immunopathologies and cancer. Extensive research focusing on discovering CCR2 and CCR5 orthosteric antagonists, ultimately resulted in some clinical success, but the area of intracellular allosteric modulators is still underexplored and the move from orthosteric to allosteric modulation could be an interesting paradigm shift. To this end, we document the development of novel CCR2 and CCR5 intracellular allosteric antagonists through a virtual screen on a small combinatorial library derived from existing CCR2, CCR5, and CCR4 ligands. Using a molecular docking approach, the created library was screene

SUBMITTER: Essa K 

PROVIDER: S-EPMC12648652 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature