ACD856
ACD856, or ACD-856, is a tropomyosin receptor kinase TrkA, TrkB, and TrkC positive allosteric modulator which is under development for the treatment of Alzheimer's disease, depressive disorders, sleep disorders, and traumatic brain injuries. It is taken by mouth.
Pharmacology
The drug potentiates the tropomyosin receptor kinases TrkA, TrkB, and TrkC with values of 382nM, 295nM, and ~330nM, respectively. As a positive allosteric modulator of TrkA and TrkB, ACD856 potentiates the effects of brain-derived neurotrophic factor and nerve growth factor.In addition to the tropomyosin receptor kinases, ACD856 is also a similarly potent positive allosteric modulator of certain other receptor tyrosine kinases, including the insulin-like growth factor 1 receptor and the fibroblast growth factor receptor 1. However, its efficacies at the IGF1R and FGFR1 were much lower than at the TrkA, TrkB, and TrkC.
In animals, ACD856 has been found to reverse scopolamine- and dizocilpine -induced memory impairment, to improve age-related memory deficits, and to have sustained antidepressant-like activity. It has also been reported to possess neuroprotective properties.
In humans, the drug has been shown to cross the blood–brain barrier and to induce dose-dependent changes in electroencephalogram parameters. No significant tolerability or safety concerns have been identified in preclinical research or phase 1 clinical trials. The drug's clinical pharmacokinetics have been characterized and its elimination half-life is approximately 19hours.