Artificial intelligence-aided discovery of prolyl hydroxylase 2 inhibitors to stabilize hypoxia inducible factor-1? and promote angiogenesis

From ZINC database with a total of 1.8 million small molecules, four compounds are identified as prolyl hydroxylase 2 inhibitors through a virtual screening workflow that sequentially incorporates machine learning, molecular docking, and molecular dynamics. Among them, compound 103 , ( E )-5-(5-((2-(1 H tetrazol-5-yl)hydrazineylidene)methyl)furan-2-yl)isoindoline-1,3-dione, promotes the migration and capillary tube formation capacity of human umbilical vein endothelial cells through enhancing the stability of hypoxia inducible factor-1 alpha and increasing the level of vascular endothelial growth factor. (c) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.