Fluorescent CDK Inhibitors for the Treatment and Diagnosis of Cancer

Categories: “Diagnostics” “Cancer Therapeutics“

Reference #: 2008-022

OTC Contact: Ruchika Nijhara, Ph.D., MBA, CLP (Directory Information | Send a Message)

Description

The invention describes promising new fluorescent small molecule pharmaceutical leads for the treatment of cancer by inhibition of cyclin dependant kinase (CDK). The novel compounds are more potent than known CDK inhibitors, purvalanols A and B as well as phase II clinical drug candidate, roscovitine (seliciclib). These compounds are especially potent inhibitors of CDK2 isoforms and effectively arrest tumor cells in the G2/M phase. These new compounds may be an effective new tool for not only for treating, but also diagnosing cancer and monitoring cancer therapy.

Applications

• Potential therapeutics for treating cancer
• Diagnosis of cancer
• Monitoring cancer therapy

Advantages

• Compounds of the invention demonstrate higher % inhibition of CDK2/A and CDK2/E than known CDK2 inhibitor, seliciclib
• A fluorescent label allow these compounds to be used as both a therapeutic to treat cancer and a diagnostic to detect cancerous cells and monitor treatment
• Cell growth inhibition potency (IC50) in certain cancer cell lines is superior to known CDK inhibitors purvanalol and seliciclib

Stage of Development

Growth inhibition, IC50 values were obtained for compounds using the 48 hours WST-1 assay in ER negative and ER positive breast cancer cell lines. Inhibition of cell cycle protein kinases: CDK1/B, CDK2/A, CDK2/E, CDK3/E and CDK7/CyclinH/MATI, by compounds of the invention were compared with commercially available CDK inhibitors purvalanols A and B and roscovitine. The compounds almost completely inhibited CDK2/E at nanomolar range. Fluorescence micrographs of breast cancer cell cultures showed that the compounds localized in the cancer cells.

inventors

Milton Brown and Venkana Yenugonda

Patent Status

Applications are pending