Inhibitors of KATs: potential therapeutic molecules
Through a rational design approach, the natural compound small molecule modulators of epigenetic enzymes (KATs) and derivatives of these molecules were tested in vitro and in vivo for their efficacy and specificity.The promising candidates have yielded molecules such as LTK14, a p300-specific inhibitor, which could repress HIV replication (Mantelingu K et al., 2007). CTK7A is another natural compound-derived KAT inhibitor that could suppress p300 autoacetylation and hence its activity, showing promising results in inhibiting histone acetylation in oral cancer and thereby the xenograft tumor growth (Arif M et al., 2010). Many other molecules, such as Luteolin, Garcinol have also shown promising therapeutic results in cancer cell lines and xenograft models (Selvi BR et al., 2015) (Balasubramanyam K et al., 2004) (Sethi G et al., 2014). Selective inhibition of p300 catalysed histone lysine butyrylation by LTK-14A without affecting its canonical acetyltransferase activity leads to inhibition of adipogenesis and attenuation of obesity (Bhattacharya et al., 2022).
Dr. K. Mantelingu, Dr. Swaminathan Venkatesh, Dr. Mohammed Arif, Dr. Ruthrotha Selvi B, Dr.Amrutha Swaminathan, Dr. Aditya Bhattacharya
