LIN28-Targeting Chromenopyrazoles and Tetrahydroquinolines Induced Cellular Morphological Changes and Showed High Biosimilarity with BRD PROTACs.

ABSTRACT: The probing of small molecules with heterocyclic scaffolds covering unexplored chemical space and the evaluation of their biological relevance are essential parts of forward chemical genetics approaches and for the development of potential small-molecule therapeutics. In this study, we profiled sets of chromenopyrazoles (CMPs) and tetrahydroquinolines (THQs), originally developed to target the protein-RNA interaction of LIN28-let-7, in a cell painting assay (CPA) measuring cellular morphological changes. Selected LIN28-inactive CMPs and THQs induced cellular morphological changes to different extents. The most CPA-active CMPs 2 and 3 exhibited high bio-similarity with the LCH and BET clusters, while the most CPA-active THQs 13 and 20 indicated a mechanism of action beyond the currently est

SUBMITTER: Jiang M 

PROVIDER: S-EPMC11694606 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature