Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA viabis-alkylation of DNA @ N7-guanine and N4-cytosine. DM-CHOC-PEN has completed Phase I/II studies as a single agent and as a radiosensitizer in subjects with cancers involving the CNS [AACR #CT129, 2016; CT069, 2019]. The current presentation reviews in vitro data that support DM-CHOC-PEN’s ability to under go polarization in a magnetic field with enhanced release in situ of the active alkylating specie – demethylpenclomedine (DM-PEN) improving cell kill – a potential enhancer for cancer management. Methods: Human non-small cell lung cancer (NSCLC) adenocarcinoma cells (H-2086) were obtained from ATCC (Manassas, VA) and maintained in tissue culture – 1640 RPMI with L-glutamine plus 10% FBS and 5% antibiotic-antimycotic solution (Sigma) in a moist 5% CO2 atmosphere @ 37oC. NSCLC cell cultures (106 cells/mL) in plates (5 cm dia.) were exposed for 24-72 hrs. to magnets (MagnetTM) that generated magnetic field strengths of 85 -110 mT. The plated cultures were treated with DM-CHOC-PEN (0.25, 0.4 & 1.0 µg/mL) +/- magnetic field exposure and monitored for cell survival and growth characteristics. Results: The in vitro studies revealed: DM-CHOC-PEN (0.25 µg/mL) alone produced an IC35vs. NSCLC cells, while a magnetic field force (110 mT) alone had no effect on cell growth. In combination - DM-CHOC-PEN (0.25 µg/mL) plus a magnetic field force (110 mT) added 48 hrs post-drug exposure produced a cell kill of 100%. Thus, in combination – drug (0.25 µg/mL) plus a magnetic field force of 110 mTimproved the therapeutic effort, as compared to either treatment alone. Release of DM-PEN was quantitated in the culture medium +/- magnetic field exposure. Drug dose exposure vs. responses will be discussed.Conclusion: DM-CHOC-PEN is polarized in a magnetic field with shifting of electron flux toward the polychlorinated pyridine ring and weakening the carbonate link facilitating its reactivity with H2O (hydrolysis) and the loss of the cholesteryl carbonate moiety, resulting in the release of the active specie – DM-PEN. DM-PEN is involved in DM-CHOC-PEN’s second phase of DNA alkylation. Thus, the ‘controlled release’ of the active specie in magnetic fields potentiates cytotoxicity and ultimately may reduce the amount of drug required for effective anti-cancer activity. Supported by – NCI/SBIR grants - R43/44CA132257 and NIH NIGMS 1 U54 GM104940 – the latter funds the Louisiana Clinical and Translational Science Center.

Citation Format: Lee Roy Morgan, Ryen Smith, Branko Jursic, Roy S Weiner, Andrew H Rodgers. Support for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) as a magnetic field effort sensitizer in NSCLC [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A098. doi:10.1158/1535-7163.TARG-19-A098