TCS HDAC6 20b is a potent and selective inhibitor of histone deacetylase 6 (HADC6) [1].
Histone deacetylases (HADC) are a series of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone and make the histones to wrap the DNA more tightly, which prevent transcription. Mutation of HADC6 is associated with Alzheimer's disease.
In HCT116 cells, TCS HDAC6 20b increased ɑ-tubulin acetylation in a dose-dependent way without a significant increase in acetylated histone H4, which indicated that TCS HDAC6 20b selectively inhibit HDAC6 [1]. Treatment human colon cancer HCT116 cells with TCS HDAC6 20b (5 μM) and paclitaxel (PTX) (0.03 μM) inhibited cells growth by approximately 50%, which suggested that TCS HDAC6 20b has potential as drug candidates when used with PTX. In estrogen receptor ɑ (ERɑ) -positive breast cancer MCF-7 cells, treatment with 17β-estradiol (E2) (1 nM) increased cell growth by 40%, which was significantly blocked by TCS HDAC6 20b [2].
References:
[1]. Suzuki T, Kouketsu A, Itoh Y, et al. Highly potent and selective histone deacetylase 6 inhibitors designed based on a small-molecular substrate. J Med Chem, 2006, 49(16): 4809-4812.
[2]. Itoh Y, Suzuki T, Kouketsu A, et al. Design, synthesis, structure--selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhibitors. J Med Chem, 2007, 50(22): 5425-5438.