Mak, Jeffrey Y. W. published the artcileHDAC7 Inhibition by Phenacetyl and Phenylbenzoyl Hydroxamates, Application of 4-Methoxyphenylacetic acid, the main research area is HDAC7 inhibitors catalytic site phenylbenzoyl hydroxamates phthalimide stability solubility.
The zinc-containing histone deacetylase enzyme HDAC7 is emerging as an important regulator of immunometabolism and cancer. Here, we exploit a cavity in HDAC7, filled by Tyr303 in HDAC1, to derive new inhibitors. Phenacetyl hydroxamates and 2-phenylbenzoyl hydroxamates bind to Zn2+ and are 50-2700-fold more selective inhibitors of HDAC7 than HDAC1. Phenylbenzoyl hydroxamates are 30-70-fold more potent HDAC7 inhibitors than phenacetyl hydroxamates, which is attributed to the benzoyl aromatic group interacting with Phe679 and Phe738. Phthalimide capping groups, including a saccharin analog, decrease rotational freedom and provide hydrogen bond acceptor carbonyl/sulfonamide oxygens that increase inhibitor potency, liver microsome stability, solubility, and cell activity. Despite being the most potent HDAC7 inhibitors to date, they are not selective among class IIa enzymes. These strategies may help to produce tools for interrogating HDAC7 biol. related to its catalytic site.
Journal of Medicinal Chemistry published new progress about Drug metabolism (metabolic stability). 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Application of 4-Methoxyphenylacetic acid.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem