RM-3-22 is a TAZQ-based hydroxamic acid derivative and potent HDAC inhibitor with IC50 of 49.9 nM, 68.5 nM, and 12.9 nM for HDAC1, HDAC3, and HDAC6 isoforms respectively.
RM-3-22 displays 97, 126-, 47-, 316-, and 334-folds higher selectivity towards HDAC6 isoform in comparison to HDAC2, HDAC4, HDAC5, HDAC7, and HDAC9, respectively.
RM-3-22 induces the cytotoxicity of different cancer cell lines, especially the lung cancer cell line A549 (IC50=0.8 uM).
RM-3-22 induces autophagy pathway through the inhibition of PI3K/Akt/mTOR.
RM-3-22 significantly induces caspase-dependent apoptosis in A549 cells.
RM-3-22 treatment causes cell cycle arrest in the G2/M phase by the disruption of cyclin B and CDC2 in A549 cells.
RM-3-22 enhances the expression of the tumor suppressor gene FTH1, which is positively correlated with apoptosis and autophagy pathway.
RM-3-22 suppresses tumor growth by inducing autophagy, apoptosis, cell cycle arrest, and FTH1 upregulation.