Development of modulators targeting G proteincoupled receptors using a combination of conventional drug discovery methodologies and artificial intelligence techniques

Abstract

Lysophosphatidic acid receptor 1 (LPA1) is one of six G protein-coupled receptors (GPCRs) in the LPA receptor family (LPA1-6) and is activated by lysophosphatidic acid (LPA). LPA1 is involved in a wide range of cellular activities, including the regulation of cell proliferation, migration, invasion, and apoptosis. Numerous studies have reported its implication in the initiation, progression, and metastasis of breast cancer. Bioinformatic analysis has also revealed the role of LPA1 in breast cancer. However, the current repertoire of LPA1 ligands targeting cancer remains highly limited, and only one LPA1 radioligand for positron emission tomography (PET) imaging of pulmonary fibrosis has been reported so far. Therefore, the objective of this study is to develop novel LPA1 antagonists and LPA1 radioligands for breast cancer therapeutics and diagnosis. [...]