Novel compounds allowing for optical detection and targeting of Choline Kinases for cancer treatment.
Choline Kinase (ChoK) deregulation is associated with oncogenesis and tumor progression in a number of human cancers, including glioblastoma, breast, and lung cancers. In breast cancer, elevated ChoK activity is correlated with histological tumor grade, resistance to antiestrogen therapies, and poor prognosis. Overexpression of ChoK alone is sufficient to induce malignant transformation.
The Delikatny Lab at the University of Pennsylvania has developed and synthetized novel cancer theranostics – therapeutics that can also serve as diagnostics – molecules based on ChoK Inhibitors. These small fluorescent molecules used at low doses can be effective as agents to image the status of tumor choline metabolism, at higher doses they can serve as inhibitors of tumor growth.
- Lower toxicity and higher selectivity compared to existing ChoK inhibitors
- Fluorescence in the NIR range is suitable for detection of ChoK in vivo
- Fluorescence in the NIR range has lower light scattering interference from hemoglobin, fat and water
- Quantitative detection of ChoK reflecting tumor aggressiveness
- Diagnostic: fluorescent detection of ChoK in animal models of cancer and human patients
- Therapeutic: inhibition of ChoK in ChoK overexpressing tumors
- Measurement of response to therapy in ChoK overexpressing tumors
- Tumor imaging agent that could be used for intraoperative imaging during cancer surgeries
Stage of Development:
- 12 compounds synthesized and prototype compounds tested in vitro
- In vivo studies performed on lead compound
- Medicinal chemistry studies are underway
- A number of in assays evaluating activity of ChoK based on 14C phosphorylation, magnetic resonance spectroscopy, nearinfrared optical imaging have been developed