biostudies-literatureUnknown9(1)Le HTTPurinergic receptor is a potential drug target for neuropathic pain, Alzheimer disease, and prostate cancer. Focusing on the structure-based ligand discovery, docking analysis on the crystal structure of P2Y₁ receptor (P2Y₁R) with 923 derivatives of 1-indolinoalkyl 2-phenolic compound is performed to understand the molecular insights of the receptor. The structural model identified the top novel ligands, 426 (compound 1) and 636 (compound 2) having highest binding affinity with the docking score of -7.38 and -6.92. We have reported the interaction efficacy and the dynamics of P2Y₁R protein with the ligands. The best hits synthesized were experimentally optimized as a potent P2Y₁ agonists. These ligands exhibits anti-proliferative effect against tScientific reports18938https://www.ebi.ac.uk/biostudies/studies/S-EPMC6908675biostudies-literatureSynthesis and preclinical validation of novel P2Y1 receptor ligands as a potent anti-prostate cancer agent.PMC6908675Murugesan ACandeias NRRimpilainen TYli-Harja OKandhavelu MKonda Mani SLe HTTfalseSynthesis and preclinical validation of novel P2Y1 receptor ligands as a potent anti-prostate cancer agent.Purinergic receptor is a potential drug target for neuropathic pain, Alzheimer disease, and prostate cancer. Focusing on the structure-based ligand discovery, docking analysis on the crystal structure of P2Y₁ receptor (P2Y₁R) with 923 derivatives of 1-indolinoalkyl 2-phenolic compound is performed to understand the molecular insights of the receptor. The structural model identified the top novel ligands, 426 (compound 1) and 636 (compound 2) having highest binding affinity with the docking score of -7.38 and -6.92. We have reported the interaction efficacy and the dynamics of P2Y₁R protein with the ligands. The best hits synthesized were experimentally optimized as a potent P2Y₁ agonists. These ligands exhibits anti-proliferative effect against t2019-01-01T00:00:00Z2019 Dec2026-05-01T20:18:43.893Z2020-05-21T23:28:35ZS-EPMC69086753183176110.1038/s41598-019-55194-8