4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), a non-neurotoxic derivative of penclomidine, is under development by Dekk-Tec for the intravenous treatment of solid tumours. DM-CHOC-PEN is a cholesterol carbonate derivative of 4-demethylpenclomedine with potential antineoplastic alkylating activity. Upon intravenous administration of 4-demethylcholesteryloxycarbonylpenclomedine, the carbonium moiety binds to and alkylates DNA at the N7 guanine position, thereby causing DNA crosslinks. This prevents DNA replication, inhibits cellular proliferation and triggers apoptosis. In addition, due to its lipophilic cholesteryl moiety this agent is able to cross the blood brain barrier (BBB) and therefore can be given intravenously compared to other alkylating agents that need to be given intra-cranially. DM-CHOC-PEN has undergone a Phase I study (allowed enrollment of subjects with advanced cancer +/- CNS involvement) and is being evaluated in a Phase II trial in subjects with advanced cancer involving the brain. DM-CHOC-PEN has completed Phase I/II trials in humans with primary and secondary tumors involving the brain with success. Complete remissions in both primary astrocytoma and metastatic lung and leukemia malignancies.Impressive objective responses and improved PFS/overall survival have been observed in subjects with NSCLC involving the CNS.