TC-2153

TC-2153 is a small molecule, brain-penetrant, selective inhibitor of STriatal-Enriched protein tyrosine Phosphatase (STEP, encoded by the PTPN5 gene). Discovered through a collaborative effort led by researchers at Yale University, TC-2153 acts by forming a reversible covalent bond with the catalytic cysteine residue in the active site of STEP. By inhibiting STEP, TC-2153 prevents the dephosphorylation and subsequent internalization of key synaptic proteins, including NMDA receptor subunits (such as GluN2B) and AMPA receptor subunits (such as GluA2), as well as downstream kinases like ERK1/2 and Pyk2. Preclinical studies have demonstrated that TC-2153 can reverse cognitive and synaptic deficits in animal models of Alzheimer's disease, Fragile X syndrome, schizophrenia, and Parkinson's disease, and can reduce hippocampal network excitability and seizure propensity in models of temporal lobe epilepsy. However, due to its reactive benzopentathiepin scaffold, which can interact with cellular protein thiol groups and modify DNA, TC-2153 is primarily utilized as a preclinical research tool rather than being advanced into clinical development.

Other names

8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride8-(trifluoromethyl)benzo[f][1,2,3,4,5]pentathiepin-6-amine8-(trifluoromethyl)benzo[f][1,2,3,4,5]pentathiepin-6-amine hydrochloride