Novel Gamma-Secretase Inhibitors for Treatment of Cancer


Summary of Invention

The investigators have discovered a unique class of gamma-secretase inhibitors that have demonstrated significant anti-cancer activity. Using a proprietary, high-throughput screening assay, the investigators identified GSI-34, a class of compounds structurally distinct from other GSIs currently utilized in clinical trials. Gamma-secretase inhibitors disrupt the Notch signaling pathway, which is involved in cell-to-cell communication and gene regulation, and is abnormally activated in many types of cancers, including chronic lymphocytic leukemia, diffuse large B-cell lymphoma, and breast cancer.

Studies have demonstrated that GSI-34 effectively blocks the migration and invasion of aggressive breast cancer cell lines.  Furthermore, GSI-34 reduced primary tumor burden in a breast cancer mouse model, and had a profound effect on lung metastasis. The investigators are now planning preclinical toxicity/tolerance studies to support IND application.


GSI-34 outperforms other GSIs currently in development in terms of anti-tumor activity

Market Opportunities

The breast cancer market size is approximately $10.2B. The leukemia therapeutics market (ALL, CLL, AML, CLL) is approximately $4.0B, projected to reach $7.6B by 2018.

A number of GSIs, such as RO04929097, MK-0752, and PF3084014, are in early-stage clinical trials for the treatment of leukemia, lymphoma, and advanced solid tumors, however, no GSIs are currently on the market.

Areas of Application

Leukemia, lymphoma, breast cancer

Patent Information

PCT application number PCT/US2009/068937 filed on December 21, 2009; National Stage filings pending in Europe, Japan, and Hong Kong; U.S. issued patent 9,056,857 (June 2015)

Lead Investigator

Dr. Yueming Li, PhD, Molecular Pharmacology & Chemistry Program, Memorial Sloan Kettering

Contact Information

Eileen Flowers, PhD
Licensing Manager
Tel: 646-888-1067

Stage of Development

Animal studies