Rocaglamide | TNFalpha inhibitor

Rocaglamide (84573-16-0) is a potent inhibitor of NFκB in T-lymphocytes with almost complete inhibition at 200nM.¹  It was able to completely inhibit IL-4 and IFN-γ production and suppress 60-85% of IL-2 and TNF-α production at 50nM in T-cells without inhibiting AP-1 and NF-κB (conversely, at concentrations <100nM, it was shown to increase NF-κB activity).²  Immunosuppression activity was due to inhibition of cytokine gene expression via blocking of NF-AT activity and is a different mechanism than suppression via Cyclosporine A and FK-506. Rocaglamide has anti-cancer properties via various pathways including ERK inhibition³, ATM/ATR-Chk1/Chk2 activation⁴, and p38 and JNK activation⁵.

References/Citations:

1) Baumann et al. (2002), Rocaglamide Derivatives Are Potent Inhibitors of NF-kB Activation in T-cells; J. Biol. Chem. 277 44791
2) Prolsch et al. (2005), Rocaglamide Derivatives Are Immunosuppressive Phytochemicals That Target NF-AT Activity in T Cells; J. Immunol. 174 7075
3) Polier et al. (2012), The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin1 and 2; Chem. Biol. 19 1093
4) Neumann et al. (2014), The natural anticancer compound rocaglamide selectively inhibits the G1-S phase transition in cancer cells through the ATM/ATR-mediated Chk1/2 cell cycle checkpoints; Int. J. Cancer 134 1991
5) Zhu et al. (2007), The traditional Chinese herbal compound rocaglamide preferentially induces apoptosis in leukemia cells by modulation of mitogen-activated protein kinase activities; Int. J. Cancer 121 1839