FSC-231 (1215849-96-9) is the first small-molecule inhibitor of the PDZ domain in protein interacting with C kinase 1 (PICK1). Binds to PICK1 PDZ domain with affinity similar to that of the endogenous peptide ligands (Ki~10.1 μM). Does not bind to PDZ domains of postsynaptic density protein 95 (PSD-95) nor glutamate receptor interacting protein 1 (GRIP1).? Pretreatment of cultured hippocampal neurons inhibits coimmunoprecipitation of the AMPA receptor GluR2 subunit with PICK1. FSC231 accelerated recycling of fluorophore-tagged GluR2 in hippocampal neurons after internalization in response to NMDA receptor activation. Blocks the expression of both long-term depression and long-term potentiation.1,2 Attenuates cocaine seeking in a rodent model.3 Blocks PICK1-induced anti-inflammatory effect in acute liver injury.4
1) Thorsen et al. (2010), Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD; Proc. Natl. Acad. Sci. USA, 107 413
2) Tang et al. (2013), Willed-movement training reduces motor deficits and induces a PICK1-dependent LTD in rats subjected to focal cerebral ischemia; Behav. Brain Res., 256 481
3) Schmidt et al. (2013), Stimulation of mGluR5 in the accumbens shell promotes cocaine seeking by activating PKC gamma; J. Neuroscience, 33 14160
4) Xie et al. (2016), PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization; Biochemie, 127 121
