calcineurin

Magnoloside A (Magloside A) is a phenylethanol glycoside from M. obovata Thunb, a calmodulin phosphatase inhibitor.

Cyclosporin A is a naturally occurring cyclic polypeptide that is the active metabolite of a fungus. Cyclosporin A is an immunosuppressant that binds to procyclins and inhibits calcineurin (IC50=7 nM).

Tacrolimus monohydrate (LCP-Tacro) is a macrolide from the culture broth of a strain of Streptomyces tsukubaensis, binds to FK506 binding protein (FKBP) to form a complex. Tacrolimus inhibits calcineurin phosphatase, which inhibits T-lymphocyte signal transduction and IL-2 transcription. Immunosuppressive properties. It prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro and has strong immunosuppressive activity in vivo.

1. (±)-Praeruptorin A could exhibit its anti-osteoclastogenic activity by inhibiting p38 Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca(2+) oscillation 2. Praeruptorin A has the potential to inhibit migration fusion of preosteoclasts in vitro and bone erosion in vivo by targeting calmodulin and inhibiting the Ca(2+) calmodulin-CaMKIV-CREB-NFATc1 and or Ca(2+) calmodulin-calcineurin-NFATc1 signaling axis. 3. Praeruptorin A and praeruptorin C can significantly upregulate multidrug resistance-associated protein 2 expression via the constitutive androstane receptor-mediated pathway in vitro, and this should be taken as an herb-drug interaction.

Isogarcinol is a natural polyisoprenylated benzophenone first isolated from plant species in the genus Garcinia. It has immunosuppressant actions, inhibiting the protein phosphatase calcineurin (IC50 = 36 μM) and suppressing the proliferation of T cells. Oral administration of isogarcinol in mice decreases delayed type hypersensitivity, prolongs graft survival in allogeneic skin transplants, suppresses inflammation in collagen-induced arthritis, and reduces clinical symptoms in experimental autoimmune encephalomyelitis. Isogarcinol inhibits the proliferation of HL-60 and PC-3 cancer cells (IC50s = 4 and 8 μg ml, respectively) through cell cycle arrest and apoptosis.

Dibefurin is a metabolite that inhibits the activity of calcineurin, a calcium calmodulin-dependent protein phosphatase involved in the activation of T lymphocytes.

Praeruptorin A ((+)-Praeruptorin A) has the potential to inhibit migration fusion of preosteoclasts in vitro and bone erosion in vivo by targeting calmodulin and inhibiting the Ca(2+) calmodulin-CaMKIV-CREB-NFATc1 and or Ca(2+) calmodulin-calcineurin-NFATc1 signaling axis.

Ascomycin (Immunomycin)(Immunomycin, FR-900520, FK520) is an ethyl analog of tacrolimus (FK506) with strong immunosuppressant properties.