LPPM-8 is a ligand for Med25 and acts as an inhibitor of Med25 protein-protein interactions (PPI). It engages with Med25 via the H2 surface of its activator-interaction domain, thereby stabilizing full-length proteins in the cellular proteome. LPPM-8 is an orthosteric inhibitor of H2-binding transcription activators (e.g., ATF6a). Med25 plays a role in the transcriptional regulation of RNA polymerase II-dependent genes and can form a transcription complex with ATF6α. LPPM-8 is valuable for studying the complex biology of Med25 and its Mediator complex.