TBK1-IN-1

TBK1-IN-1 (also known as compound 7l) is a potent, selective, and ATP-competitive small-molecule inhibitor of TANK-binding kinase 1 (TBK1) with an IC50 value of 22.4 nM. Originally designed as a pyrrolo[2,3-d]pyrimidine derivative using deep generative modeling by researchers at Jinan University and the Shanghai Institute of Materia Medica, TBK1-IN-1 inhibits the expression of TBK1 downstream target genes such as CXCL10 and IFN-beta. In addition to its role as a TBK1 inhibitor, virtual screening identified TBK1-IN-1 as an inhibitor of the palmitoyltransferase ZDHHC17. By targeting ZDHHC17, TBK1-IN-1 blocks the palmitoylation and subsequent nuclear translocation of D-2-hydroxyglutarate dehydrogenase (D2HGDH), thereby preventing epigenetic reprogramming and lipid accumulation in hepatocytes. Consequently, TBK1-IN-1 has demonstrated therapeutic efficacy in alleviating metabolic dysfunction-associated steatohepatitis (MASH) in both in vitro and in vivo models.

Other names

compound 7lcompound7lcompound-7lTBK1 inhibitor 7lTBK-1 inhibitor 7lTBK 1 inhibitor 7l