HDAC1 activator-1

HDAC1activator-1 is a selective HDAC1 activator with oral bioavailability, exhibiting no significant effects on other HDAC family members. It possesses neuroprotective properties, improving cognitive and motor function deficits by reducing neuronal loss and gliosis. In the human neuroblastoma cell line SH-SY5Y, HDAC1activator-1 specifically activates HDAC1, inhibiting abnormal cell cycle progression and alleviating DNA damage. This compound is applicable for research on neurodegenerative diseases associated with TDP43 protein, such as amyotrophic lateral sclerosis (ALS), and in studies related to ischemic brain injury.

HDAC1 Activator-1 dose-dependently enhances HDAC1 enzyme activity and is highly selective for HDAC1, showing no significant effects on HDAC2, HDAC3, and HDAC8. It specifically activates HDAC1 in vitro in the human neuroblastoma cell line SH-SY5Y. Furthermore, HDAC1 Activator-1 (2.5 μM, 25 μM) can restore HDAC1 enzyme activity in primary cortical neurons subjected to oxygen-glucose deprivation (OGD).

HDAC1 Activator-1 has been evaluated in FTLD-TDP transgenic mice at doses of 0.3, 6, and 30 mg/kg, administered intraperitoneally, five days a week for one month. The 6 and 30 mg/kg dosages demonstrated the ability to restore cognitive and motor functions as well as nuclear HDAC1 activity. Further, a 6 mg/kg dose given over two months improved cognitive deficits and motor dysfunctions, while reversing abnormal cell cycles, DNA damage, neuronal loss, and gliosis. Additionally, in a rat model of cerebral ischemia, a daily dose of 30 mg/kg significantly restored HDAC1 activity in brain tissue, reduced infarct volume, neuronal apoptosis, DNA damage, and oxidative stress markers, and enhanced neuromuscular, balance, and forelimb strength functions.