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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011326-03
Application #
8553107
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$85,964
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code