to support the continued development of KDAc's selective histone deacetylase 3 (HDAC3
) inhibitor programme, the company said.
In the case of the HDAC assays, there were three targets, HDAC1, HDAC3
and HDAC6, tested with 41, 2 and 3 reference chemicals, respectively.
The benzamide bifunctional molecule was found to be active for class I deacetylases (HDAC3
) and class II deacetylases (HDAC6) and was potent in nM concentration in breast cancer models.
Based on the results of siRNA transfection, cells were transfected with Hdac3
expression plasmid and subsequently mock-treated or treated with 8.0 mmol/L VPA.
The stiffness is caused by a 'molecular brake pad' called HDAC3
which has become 'overeager' in compacting the DNA.
Follicular hyperandrogenemia induces marked changes in methylation status of essential genes for reproduction and development such as PPAR[gamma], HDAC3
, and NCOR1 .
Moreover, this is supported by a recent study indicating that the expression of nuclear HDAC1, HDAC2, and HDAC3
proteins was increased in carcinomas compared with benign tumors .
Particularly, REV-ERB[alpha] and REV-ERB[beta] decrease MMP-9 expression via HDAC3
(histone deacetylase 3) .
Shen, "NF-KB/p65 antagonizes Nrf2ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3
to MafK," Biochimica et Biophysica Acta (BBA)--Molecular Cell Research, vol.
Termanini et al., "Requirement for the histone deacetylase Hdac3
for the inflammatory gene expression program in macrophages," Proceedings of the National Academy of Sciences of the United States of America, vol.
Analysis of protein-protein interaction: STRING prediction indicated that UTY interacts with heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1); heat shock protein 90 kDa alpha, class B member 1 (HSP90AB1); ubiquitin specific peptidase 9, Y-linked (USP9Y); lysine (K)-specific demethylase 5D (KDM5D); histone deacetylase 2 (HDAC2); histone deacetylase 1 (HDAC1); histone deacetylase 3 (HDAC3
); SET domain containing 2 (SETD2); DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y-linked (DDX3Y) and sex determining region Y (SRY) (Figure 4).