Tacedinaline

Tacedinaline (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name; developmental code name CI-994), also known as N-acetyldinaline, is a histone deacetylase (HDAC) inhibitor and possible cognitive enhancer which is under development for the treatment of Alzheimer's disease. It was also under development as an antineoplastic agent for the treatment of various cancers, but development for these uses was discontinued. The drug is taken orally.

Side effects

Unlike many other less-selective HDAC inhibitors, which have often produced unwanted side effects, tacedinaline is said to be well-tolerated. However, adverse effects such as thrombocytopenia among others have nonetheless been observed in cancer treatment trials.

Pharmacology

Tacedinaline is a potent inhibitor of the class I HDAC1, HDAC2, and HDAC3, with IC50Tooltip half-maximal inhibitory concentration values of 41–636 nM, 147–696 nM, and 46–472 nM, respectively. The drug showed no inhibition of other HDACs, including HDAC4 through HDAC11, at a concentration of 10,000 to 33,000 nM. It is more selective for class I HDACs compared to many other HDAC inhibitors. In addition to its HDAC inhibition, tacedinaline also activates Wnt/β–catenin signaling and hence is said to have a dual mechanism of action. It enhances synaptogenesis, increases central brain-derived neurotrophic factor (BDNF) expression, and decreases tau phosphorylation in preclinical research. Tacedinaline enhances cognition and memory in rodents.