HDAC9-IN-1 is a selective class IIa HDAC inhibitor that binds to HDAC9 with an IC50 of 40 nM. HDAC9-IN-1 potently inhibits HDACs 4 and 7 while showing weak activity against HDAC6 (IC50 values: 180 nM ( HDAC4 ), 190 nM ( HDAC7 ), 970 nM ( HDAC6 )). HDAC9-IN-1 significantly inhibits several human cancer cells, induces apoptosis and DNA damage in human cancer cells, and modulates caspase -related proteins and p38 in human cancer cells. HDAC9-IN-1 can be used for the research of oral cancer, breast cancer, gastric cancer [1].
In Vitro, HDAC9-IN-1 (compound 7g) (5-30 min) potently inhibits HDAC 9 and class IIa HDACs 4 and 7 while showing weak activity against HDAC 6 and no activity against class I HDACs (IC50 values: 40 nM (HDAC9), 180 nM (HDAC4), 190 nM (HDAC7), 970 nM (HDAC6), >40 μM (class I))[1]. HDAC9-IN-1 (24 h) inhibits viability of cancer cells and normal lung fibroblasts (IC50 values: 3.0 μM (SCC2095), 8.4 μM (MDA-MB-231), 5.8 μM (SCM-1), 8.0 μM (normal lung fibroblasts))[1]. HDAC9-IN-1 (1-10 μM; 24-48 h) induces dose- and time-dependent apoptosis in SCC2095 cells[1]. HDAC9-IN-1 (1-10 μM; 24 h) modulates apoptotic, HDAC substrate, and stress response proteins in SCC2095 cells[1]. HDAC9-IN-1 (2.5-5 μM; 12-24 h) increases ROS generation accompanied by the increased DNA damage in SCC2095 cells in a time-dependent manner[1].
References:
[1]. Hsu KC, et al. Synthesis and biological evaluation of ortho -phenyl phenylhydroxamic acids containing phenothiazine with improved selectivity for class IIa histone deacetylases. J Enzyme Inhib Med Chem. 2024;39(1):2406025.
In Vitro, HDAC9-IN-1 (compound 7g) (5-30 min) potently inhibits HDAC 9 and class IIa HDACs 4 and 7 while showing weak activity against HDAC 6 and no activity against class I HDACs (IC50 values: 40 nM (HDAC9), 180 nM (HDAC4), 190 nM (HDAC7), 970 nM (HDAC6), >40 μM (class I))[1]. HDAC9-IN-1 (24 h) inhibits viability of cancer cells and normal lung fibroblasts (IC50 values: 3.0 μM (SCC2095), 8.4 μM (MDA-MB-231), 5.8 μM (SCM-1), 8.0 μM (normal lung fibroblasts))[1]. HDAC9-IN-1 (1-10 μM; 24-48 h) induces dose- and time-dependent apoptosis in SCC2095 cells[1]. HDAC9-IN-1 (1-10 μM; 24 h) modulates apoptotic, HDAC substrate, and stress response proteins in SCC2095 cells[1]. HDAC9-IN-1 (2.5-5 μM; 12-24 h) increases ROS generation accompanied by the increased DNA damage in SCC2095 cells in a time-dependent manner[1].
References:
[1]. Hsu KC, et al. Synthesis and biological evaluation of ortho -phenyl phenylhydroxamic acids containing phenothiazine with improved selectivity for class IIa histone deacetylases. J Enzyme Inhib Med Chem. 2024;39(1):2406025.