RO4929097

RO4929097 (RG-4733) is an orally active γ secretase inhibitor with an IC₅₀ of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC₅₀ of 14 nM and 5 nM, respectively^[1]. IC50 & Target:IC50: 4 nM (γ secretase)^[1] In Vitro:RO4929097 inhibits the production of ICN reducing the expression of the downstream Notch target, Hes1, producing a less transformed morphology in A549 cells. RO4929097 inhibits Notch processing in human tumor-derived cells^[1].RO4929097 (1 μM) inhibits the growth of breast cancer cells, and the inhibition is 20% for SUM149 and 10% for SUM190 cells. RO4929097 does not have a marked effect in invasiveness of SUM149 cells. RO4929097 significantly reduces colony formation by both cell lines with the effect being more notable in SUM149 than by SUM190 cells^[2]. RO4929097 inhibits proliferation, anchorage independent growth, and sphere formation of primary melanoma cells in vitro^[3]. In Vivo:RO4929097 (3-60 mg/kg, p.o.) results in significant tumor growth inhibition in nude mice bearing A549 NSCLC xenografts, compared with vehicle-treated animals. When mice are treated with 60 mg/kg RO4929097 twice daily with the 7+/14- schedule, treatment initially causes regression of established A549 tumors^[1]. RO4929097 impairs the growth of primary melanoma cells in vivo. The percentage of secondary tumors formed by RO4929097-treated cells is lower; the secondary tumors formed by RO4929097-treated cells are smaller; a significant delay in tumor formation by the RO4929097-treated cells compared to the vehicle-treated ones is observed in mice injected with 10⁴ cells in vivo^[3].