FKBP12.6 Activators

FKBP12.6, a member of the immunophilin protein family, plays a crucial role in the regulation of calcium release in cardiac muscle cells. It achieves this by binding to and stabilizing the ryanodine receptor 2 (RyR2), a calcium-release channel located on the sarcoplasmic reticulum. The functional activity of FKBP12.6 can be enhanced by several chemicals that influence specific signaling pathways or cellular processes directly involved in its regulation.Chemicals such as Cyclosporin A, Tacrolimus, Erythromycin, and Ascomycin bind to FKBP12.6 and inhibit calcineurin,a phosphatase that dephosphorylates RyR2. The inhibition of calcineurin indirectly enhances the stabilizing effect of FKBP12.6 on RyR2. Furthermore, Rapamycin and Sirolimus bind to FKBP12.6 and inhibit mTOR, a kinase that regulates cell growth and metabolism. This binding enhances the stabilizing effect of FKBP12.6 on RyR2. Zearalenone, a non-steroidal estrogenic mycotoxin, also enhances the stabilizing effect of FKBP12.6 on RyR2 by binding to it.

Geldanamycin and Radicicol bind to Hsp90, a chaperone protein that interacts with RyR2, indirectly enhancing the stabilizing effect of FKBP12.6 on RyR2. Tautomycin, Okadaic Acid, and Cantharidin inhibit protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), which are involved in the dephosphorylation of RyR2. By inhibiting these phosphatases, these chemicals indirectly enhance the stabilizing effect of FKBP12.6 on RyR2. Hence, these chemicals can enhance the functional activity of FKBP12.6 through their influence on specific signaling pathways or cellular processes.