RO4929097

RO4929097 is an orally bioavailable, small-molecule inhibitor of gamma secretase, a multi-subunit protease complex involved in the activation of Notch receptors. By inhibiting gamma secretase, RO4929097 blocks Notch signaling—a pathway implicated in tumor cell proliferation and survival—thereby exerting potential antitumor effects. The drug was initially developed by Roche for Alzheimer's disease but has since been primarily investigated for various cancers, including melanoma, colorectal cancer, pancreatic cancer, ovarian cancer, renal cell carcinoma (especially after anti-VEGF treatment failure), advanced brain tumors, relapsed non-small cell lung cancer (NSCLC), sarcoma, lymphoma, Wilms' tumor, and osteosarcoma[1][2][3][5][6][7]. Preclinical studies have also suggested antifibrotic activity via suppression of Notch and ERK1/2 signaling pathways[8]. Despite promising early-phase results and over 35 phase I/II trials conducted across multiple indications—including combination regimens with agents like bevacizumab—no phase III trials have commenced. Most development programs were discontinued or terminated due to lack of availability or strategic decisions[5][7].

Other names

847925-91-1