Sig-1R Inhibitors

Chemical inhibitors of Sig-1R offer a range of mechanisms by which they can inhibit the protein's function. Haloperidol, a well-characterized sigma receptor antagonist, binds directly to Sig-1R, inhibiting its activity and preventing the receptor from interacting with other signaling proteins, which is essential for its function in intracellular signaling and neuroprotection. Similarly, BD1047 and NE-100, both selective sigma receptor antagonists, inhibit Sig-1R by blocking its agonist-mediated signaling, which disrupts its role in modulating ion channel activity and calcium signaling pathways. This blockade directly inhibits the receptor's function, as it can no longer exert its effects on cellular plasticity and neuroprotection mechanisms.

Furthermore, BD1063 and Rimcazole act by binding to Sig-1R and inhibiting its interaction with other proteins and signaling molecules, crucial for its modulatory functions in the central nervous system. Progesterone, which binds to Sig-1R, can inhibit its activity when present at high concentrations by occupying the binding site, thus preventing receptor activation and subsequent signaling. SN79 acts as an antagonist at the receptor, interfering with Sig-1R's role in modulating neurotransmission and neuroplasticity. S1RA (E-52862) binds to Sig-1R, preventing its interaction with other proteins, which blocks its downstream signaling pathways. Similarly, SM-21 and PB28 serve as sigma receptor antagonists that bind to Sig-1R with high affinity, inhibiting its regulatory role in ion channel activity and neuroprotective signaling processes, directly hindering the receptor's functionality within these cellular contexts.