SMI-6860766

SMI-6860766 is an inhibitor of the protein-protein interaction between TNF receptor-associated factor 6 (TRAF6) and CD40.¹ It binds to TRAF1, TRAF2, TRAF3, and TRAF6 (K_ds = 52, 30, 37, and 59 µM, respectively). SMI-6860766 inhibits LPS-induced increases in the levels of NF-κB in RAW 264.7 macrophages (IC₅₀ = 0.3 µM). It inhibits anti-Cd40 antibody-induced increases in the levels of Il-1β and Il-6 in primary mouse bone marrow-derived macrophages (BMDMs; IC₅₀s = 5.7 and 2.4 µM, respectively). SMI-6860766 (10 µmol/kg) increases survival in a mouse model of sepsis induced by cecal ligation and puncture. It decreases blood levels of glucose and adipose tissue levels of leukocytes, T helper cells (Ths), cytotoxic T cells, and M1 and M2 macrophages in a mouse model of diet-induced obesity (DIO) when administered at a dose of 10 µmol/kg per day.²

WARNING This product is not for human or veterinary use.

1. Zarzycka, B., Seijkens, T., Nabuurs, S.B., et al. Discovery of small molecule CD40-TRAF6 inhibitors. J. Chem. Inf. Model 55(2), 294-307 (2015).

2. van den Berg, S.M., Seijkens, T.T., Kusters, P.J., et al. Blocking CD40-TRAF6 interactions by small-molecule inhibitor 6860766 ameliorates the complications of diet-induced obesity in mice. Int. J. Obes. (Lond) 39(5), 782-790 (2014).