A Natural Product Inhibitor of Cdc7 for Use in Cancer Treatment

SK1397

Summary of Invention

This invention identifies a natural product, known as MSK-777, as a highly effective cancer drug blocking the kinase Cdc7. Cdc7 is a cell-cycle regulator known to be over-expressed in many cancer types and is linked to promoting tumor formation. In a high-throughput screening against over 300 known kinases, MSK-777 was found to be highly selective for Cdc7, showing minimal or no activity against all other tested kinases.  MSK-777 has demonstrated activity against chemotherapy-resistant cell lines and other cancer cell lines, including AML, ALL, MDS, CML, glioblastoma, uterine sarcoma, mesothelioma, multiple non-small cell lung cancers, ovarian cancer, and melanoma and has been successfully tested in animal models, including hematological and solid tumors.

Large quantities of clinical-grade material have been synthesized and are currently being utilized in IND-enabling studies. MSK partnered with the Leukemia and Lymphoma Society (LLS) to further characterize this natural product and advance it to the clinic.

Advantages

MSK-777 has a low manufacturing cost and is readily sourceable. It targets a broad range of cancers and has very limited toxicity to normal cells. Other molecules targeting this kinase are ATP-mimetics that are often challenged by cross-reactivity with other kinases.

Market Opportunities

The 2011 leukemia therapeutics market (ALL, CLL, AML, CLL) was $4.0B, forecasted to reach $7.6B by 2018.  The lymphoma market could reach $10B by 2019. If this technology proves effective in treating solid tumors, it could tap into other significant markets as well.

Areas of Application

Initial indications are AML, ALL, MDS, and CML.  Additionally, in vitro and animal data indicate that this invention could work in solid tumor indications.

Stage of Development

Ongoing IND-enabling studies

Patent Information

PCT Application PCT/US2011/027619 filed 03/08/2011, now published
National Stage Entry pending in US, Canada, China, Eurasia, Europe, India, Japan, Australia

Lead Investigator

Dr. Mark Frattini, MD/PhD, Division of Hematology/Oncology, Columbia University, formerly of Memorial Sloan Kettering

Contact Information

Imke Ehlers, PhD, CLP
Senior Licensing Manager
Tel: 646-888-1074

Stage of Development

IND-ready

Indications

Types