SOMCL-668 – (1422251-09-9)

SOMCL-668 is a novel, potent, and selective allosteric modulator of the sigma-1 receptor, exhibiting significant therapeutic potential in various neurological conditions. This compound has demonstrated efficacy in attenuating acute phencyclidine (PCP)-induced hyperactivity and prepulse inhibition (PPI) disruption, as well as ameliorating social deficits and cognitive impairment caused by chronic PCP treatment. The effects of SOMCL-668 are mediated through the sigma-1 receptor, as evidenced by the blockade of its actions by the selective sigma-1 receptor antagonist BD1047 and the lack of efficacy in sigma-1 receptor knockout mice.

In vitro studies have shown that SOMCL-668 positively modulates sigma-1 receptor agonist-induced intrinsic plasticity in brain slices. Furthermore, in vivo experiments indicate that SOMCL-668 enhances the improvement in social deficits and cognitive impairment induced by the selective sigma-1 agonist PRE084. SOMCL-668 also reverses the chronic PCP-induced down-regulation of key signaling molecules such as p-AKT/AKT, p-CREB/CREB, and BDNF in the frontal cortex of wild-type mice, but not in sigma-1 knockout mice. The administration of the PI3K/AKT inhibitor LY294002 abolishes the ameliorative effects of SOMCL-668 on chronic PCP-induced schizophrenia-related behaviors by inhibiting BDNF expression.

These findings suggest that allosteric modulation of the sigma-1 receptor by SOMCL-668 may represent a novel approach for the treatment of psychotic illnesses, offering advantages in safety and selectivity.

The above information is displayed for information purpose only, and has not been reviewed by EON nor does EON attests or validates the accuracy nor does it constitutes a recommendation or validation.

Sources:

https://pubchem.ncbi.nlm.nih.gov/compound/71195187
https://www.medchemexpress.com/somcl-668.html
https://www.medkoo.com/products/41396
https://pubmed.ncbi.nlm.nih.gov/34865170/