RO4929097 (RO4929097; R4733; RO04929097)

Description: RO4929097 (also called RO-4929097; RO04929097; R-4733) is a novel, potent and orally bioavailable small molecule inhibitor of the gamma-secretase (gamma secretase-GS) with potential antitumor activity. It inhibits gamma-secretase with an IC50 of 4 nM in a cell-free assay and also inhibits cellular processing of Abeta40 and Notch (substrate for gamma-secretase) with EC50s of 14 nM and 5 nM, respectively. RO4929097 binds to GS and blocks activation of Notch receptors, which may inhibit tumor cell proliferation. Since overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth, RO4929097 has the potential to treat cancer. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains.

References: Cancer Res. 2009 Oct 1; 69(19):7672-80; Breast Cancer Res Treat. 2012 Jul; 134(2):495-510.