Discovery of a novel Fam20C inhibitor for treatment of triple-negative breast cancer.

Sequence similarity 20 family member C (Fam20C), a Golgi casein kinase, has a gradually elucidated mechanism in triple-negative breast cancer (TNBC) and is considered a possible target for therapeutic intervention. In this study, we combined virtual screening and chemical synthesis methods to obtain a new small-molecule Fam20C inhibitor, compound 5k, which possesses desirable kinase inhibitory activity against Fam20C and significant anti-proliferative activity against MDA-MB-231 and BT-549 cells. Subsequently, cellular thermal shift assay (CETSA), molecular docking, and molecular dynamics (MD) simulations revealed that compound 5k binds to Fam20C.

Targeting Death-Associated Protein Kinases for Treatment of Human Diseases: Recent Advances and Future Directions.

The death-associated protein kinase (DAPK) family is a member of the calcium/calmodulin-regulated serine/threonine protein kinase family, and studies have shown that its role, as its name suggests, is mainly to regulate cell death. The DAPK family comprises five members, including DAPK1, DAPK2, DAPK3, DRAK1 and DRAK2, which show high homology in the common N-terminal kinase domain but differ in the extra-catalytic domain. Notably, previous research has suggested that the DAPK family plays an essential role in both the development and regulation of human diseases.