Hes1 (helix-loop-helix transcription factor 1) is a downstream effector of Notch signaling and plays a crucial role in orchestrating developmental processes during the embryonic stage. Its aberrant signaling in adulthood is linked to the pathogenesis of cancer. JI051 can inhibitor Hes1 via cancer-associated protein chaperone PHB2 (prohibitin 2) and impair the ability of Hes1 to repress transcription. JI051 inhibited HEK293 cell proliferation with an EC50 of 0.3μM and induced cell-cycle arrest in G2/M at 1μM. Also it dose-dependently reduced cell growth of the human pancreatic cancer cell line MIA PaCa-2[2].
作用机制
JI051 inhibits Hes1 through binding to PHB2. It stabilizes PHB2’s interaction with Hes1 outside the nucleus.[2]
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