Gγ4 Inibidores

Os inibidores comuns de Gγ4 incluem, entre outros, Gossipol CAS 303-45-7, Toxina da tosse convulsa (proteína activadora de ilhotas) CAS 70323-44-3, NF449 CAS 627034-85-9, YM 254890 CAS 568580-02-9 e Forskolin CAS 66575-29-9.

Chemical inhibitors of Gγ4 work through various mechanisms to interrupt the normal signaling pathways in which Gγ4 participates. Gossypol, for example, binds to G protein-coupled receptors (GPCRs), altering their conformation, which in turn inhibits GPCR-mediated activation of G proteins, including Gγ4. Whooping cough toxin acts through ADP-ribosylation of the Gαi subunit of heterotrimeric G proteins, which prevents the interaction between Gαi and Gγ4, effectively inhibiting the function of Gγ4. Similarly, cholera toxin catalyzes the ADP-ribosylation of Gαs subunits. This modification leads to persistent activation of Gαs, which interrupts the regulatory cycles that would normally involve Gγ4, thus inhibiting its function.

Other inhibitors target different components of the G protein signaling pathway to inhibit Gγ4. NF449 is a selective Gαs inhibitor that prevents the binding of Gαs to Gγ4, disrupting the Gαs-Gβγ dimer required for Gγ4 activity. YM-254890 specifically inhibits Gαq function, which in turn interrupts the formation of the Gαq-Gβγ complex necessary for Gγ4 activity. Suramin antagonizes GPCRs to inhibit G protein-coupled receptor-mediated activation, which includes Gγ4. BIM-46187 inhibits G protein-coupled receptor signaling, thereby reducing the activation of associated G proteins and inhibiting the participation of Gγ4 in signal transduction. CCG-4986 selectively inhibits Regulator of G Protein Signaling 4 (RGS4), which in turn leads to inhibition of Gα-Gγ4 interactions and subsequent inhibition of Gγ4 function. AG 1478 blocks receptor tyrosine kinases that are involved in activating G protein signaling pathways, thus indirectly inhibiting Gγ4 function. Tertiapin-Q binds to and inhibits GIRK channels that are modulated by the Gβγ subunits of G proteins, indirectly affecting Gγ4 by interfering with Gβγ-mediated signaling. Finally, U73122 inhibits phospholipase C, which is vital for GPCR signaling, consequently preventing subsequent signaling that depends on G protein activation and thus indirectly inhibiting Gγ4 function.