We have executed the Materials Transfer Agreements necessary for us to obtain the 27 compounds from the NCGC. Per our agreement with NCGC, no more than 10 compounds will be sent to us at a time for testing in a blinded fashion. NCGC has also provided us with the reference 50% lethal dose (LD50) values, as determined by their assays. Using quantitative assays of intracellular ATP content (similar to those used initially by NCGC), we have confirmed our ability to replicate roughly 50% cytotoxicity at LD50 drug concentrations in culture with the first 10 compounds supplied. We have completed screening the first 10 compounds for radiation sensitizers, and this revealed that one of the 10 compounds acted as a radiosensitizer in culture. After confirmatory assays confirmed this finding, the data were reviewed with NCGC collaborators, who revealed that rapamycin was the compound exhibiting sensitization. This finding makes sense with what is known about the mTOR pathway (upon which rapamycin acts) in chordoma cells. Experiments are ongoing to elucidate the precise level and mechanism of radiation sensitization. We have received the next set of 10 compouds from NCGC for screening in blinded fashion.
