Striatal-enriched protein tyrosine phosphatase (STEP) is a CNS-rich protein associated with a variety of neurological and neuropsychiatric disorders. Firstly, it is expressed exclusively in the central nervous system. Then, it can regulate various neuronal signaling factors through the dephosphorylation of different substrates. Secondly, STEP regulates key signaling proteins required for synaptic strengthening and trafficking of NMDA and AMPA receptors. Importantly, both high and low levels of STEP disrupt synaptic function and lead to learning and behavioral deficits. In addition, scientists find high levels of STEP in Alzheimer’s disease, Parkinson’s disease, and schizophrenia, among others. Low levels of STEP activity are present in other diseases including ischemia, Huntington’s disease, alcoholism, and stress disorders, among others.
TC-2153 is a STEP inhibitor with psychotropic activity and low acute toxicity.
TC-2153 is a selective inhibitor of striatal-enriched protein tyrosine phosphatase (STEP), with psychotropic activity and low acute toxicity. It increases the expression of brain-derived neurotrophic factor (BDNF) in the brain. And it decreases MAOA and 5-HT1A receptors mRNA levels in the midbrain.
In in vitro studies, TC-2153 (10 μM; 3 h) reduces the percentage of c-fos-positive neurons induced by DOI in cortical and hippocampal neurons cultured in vitro. Besides, chronic TC-2153 (20 mg/kg; intraperitoneal injection; once daily for 7 days) treatment in vivo, shows antidepressant-like effects with no changes in locomotion, exploratory activity, and anxiety. On the other hand, acute TC-2153 (10 mg/kg and 20 mg/kg; single dose) treatment in vivo inhibits the functional activity of 5-HT2A receptors in mice. Importantly, it shows an antidepressant-like effect in the forced swim test without any adverse side effects on locomotor activity, anxiety, exploration, motor skill, and obsessive-compulsive-like behavior. Furthermore, both acute and chronic methods inhibit the functional activity of 5-HT2A receptors.
In conclusion, TC-2153 is a selective inhibitor of striatal-enriched protein tyrosine phosphatase (STEP). Moreover, it has psychoactive activity and low acute toxicity.