Preferred Label : Temozolomide Perillyl Alcohol Conjugate NEO212;
NCIt synonyms : Temozolomide-Perillyl Alcohol Conjugate NEO212; TMZ-POH NEO212; TMZ-POH Conjugate NEO212;
NCIt definition : An orally bioavailable agent composed of the prodrug and alkylating agent temozolomide
(TMZ), a triazene analog of dacarbazine, covalently conjugated to perillyl alcohol
(POH), a naturally occurring monoterpene, with potential antineoplastic activity.
Upon oral administration of temozolomide perillyl alcohol conjugate NEO212, TMZ is
converted at physiologic pH to the short-lived active compound, monomethyl triazeno
imidazole carboxamide (MTIC). MTIC is rapidly degraded into a methyldiazonium ion
that methylates DNA at the O6 and N7 positions of guanine, resulting in inhibition
of DNA replication and the induction of apoptosis. In addition, NEO212 may decrease
the focal adhesion kinase (FAK)/Src signaling pathway and the production of certain
matrix metalloproteinases (MMPs), and may block and reverse the epithelial-to-mesenchymal
transition (EMT) process. This may reduce tumor cell migration and invasion. Also,
NEO212 promotes mitochondrial dysfunction and induces mitochondrial apoptosis, inhibits
the nuclear translocation of transcription factor EB (TFEB), and impairs the lysosomal
function and blocks the autophagy flux in susceptible tumor cells. Like TMZ, NEO212
crosses the blood-brain-barrier (BBB). Compared to TMZ alone, NEO212 stabilizes the
prodrug TMZ, and allows better BBB penetration, greater cellular uptake and increased
potency.;
Molecule name : NEO 212; NEO-212;
Origin ID : C211529;
concept_is_in_subset
- has_target
