EG-011 (WASP activator EG-011, EG011) is a first-in-class, small molecule activator of the auto-inhibited form of Wiskott-Aldrich syndrome protein (WASp) with selective anti-tumor activity in lymphomas.
The anti-tumor activity of EG-011 was maintained in the resistant cell line derived from the MZL VL51 with secondary resistance to ibrutinib (IC50: 500 nM in both parental and resistant), while it was higher in the MZL model with resistance to PI3Kdelta inhibitor derived from VL51 (IC50: 100 nM).
The copanlisib-resistant MZL VL51 (IC50: 2 μM) and Karpas1718 idelalisib-resistant (5 nM) showed a slightly decreased sensitivity to EG-011 (Karpas1718 parental, IC50: 1 nM).
The AMO-1 carfilzomib resistant cell line showed an IC50 to EG-011 treatment that was more than 20 times lower that the carfilzomib sensitive parental cell line (IC50: 250 nM vs 6 μM).
EG-011 is a novel small molecule with in vitro and in vivo anti-tumor activity against lymphoma and acute leukemias, but, at least so far, no activity in solid tumor models (Gaudio et al AACR 2019).