PSP Inhibitors

Chemical inhibitors of PSP can exert their inhibitory effects through various biochemical pathways. Lithium chloride, SB216763, and indirubin-3'-monoxime share a common mechanism of action by targeting and inhibiting glycogen synthase kinase-3 (GSK-3). This kinase is known to phosphorylate PSP, leading to its functional inactivation. By inhibiting GSK-3, these chemicals ensure that PSP remains in a dephosphorylated, active state within the cell. Similarly, kenpaullone serves as a dual inhibitor of both GSK-3 and cyclin-dependent kinases (CDKs), which may also target PSP for phosphorylation. The inhibition of these kinases by kenpaullone consequently prevents the phosphorylation of PSP, thereby sustaining its activity. Additionally, paullones and roscovitine, primarily known as CDK inhibitors, can also maintain the activity of PSP by preventing its phosphorylation through the inhibition of CDKs that are capable of modifying PSP.

Furthermore, chemicals like SP600125 and LY294002 disrupt other signaling pathways that intersect with PSP activity. SP600125 inhibits the c-Jun N-terminal kinase (JNK), which can phosphorylate PSP directly or indirectly affect its activity, leading to inhibition. LY294002, as a PI3K inhibitor, blocks the PI3K-Akt signaling pathway, which may activate kinases involved in PSP's phosphorylation. Rapamycin and wortmannin act similarly by inhibiting the mTOR and PI3K pathways, respectively. The inhibition of these pathways by rapamycin and wortmannin prevents the activation of downstream kinases that could phosphorylate and inactivate PSP. Lastly, PD98059 and U0126, both MEK inhibitors, disrupt the MAPK/ERK pathway, which is another potential route for the phosphorylation and inactivation of PSP.