MI353 (A-582941) (CAS No.:848591-90-2) is a potent, selective and brain-penetrant partial agonist of α7 nAChR

MI353, also known as A-582941, is a novel and selective α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator. It has shown promising potential in the treatment of cognitive impairment associated with Alzheimer's disease and other neurological disorders.

The α7 nAChR is a subtype of the nAChR family that is predominantly expressed in the central nervous system (CNS). It plays a critical role in cognition, learning, and memory. Enhancing the activity of α7 nAChR could potentially improve cognitive function in patients with neurological disorders.

MI353 acts by binding to a specific site on the α7 nAChR known as the orthosteric site. This allosteric modulation of the receptor leads to an increase in synaptic transmission and enhances the sensitivity of the receptor to acetylcholine, a key neurotransmitter in the CNS.

Preclinical studies have demonstrated that MI353 is effective in improving cognitive function in animal models of Alzheimer's disease and schizophrenia. Moreover, MI353 has shown a favorable safety profile and no significant adverse effects in preclinical studies.

Several clinical trials have been conducted to evaluate the safety and efficacy of MI353 in humans. In a phase I clinical trial, MI353 was shown to be safe and well-tolerated, with no serious adverse events reported. A phase II clinical trial is currently underway to evaluate the cognitive efficacy of MI353 in patients with mild to moderate Alzheimer's disease.

In conclusion, MI353 is a promising drug candidate for the treatment of cognitive impairment associated with neurological disorders. Its selective action on the α7 nAChR and favorable safety profile make it a potentially effective and safe treatment option. Further clinical studies are required to determine its long-term safety and efficacy in human subjects.

References:

1. Ondrejcak T, et al. CNS Neurol Disord Drug Targets. 2014;13(9):1546-57.

2. Olincy A, et al. Neuropsychopharmacol. 2019;44(4):683-90.

3. ClinicalTrials.gov. Identifier: NCT03548606. Accessed March 22, 2021.