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Dacarbazine


Mechanism of action:

Dacarbazine is an alkylating agent and a triazene derivative. Dacarbazine itself is inactive and must be metabolized in the liver by the cytochrome P450 system to form the active intermediate MTIC (5-(3-methyl-1-triazeno)imidazole-4-carboxamide). MTIC methylates DNA, with the O⁶ position of guanine being especially critical, although the N⁷ position can also be affected. This interferes with DNA replication and causes mispairing, ultimately triggering apoptosis due to extensive DNA damage.

Reference(s):

Lonn U et al. (1987). Prevention of dacarbazine damage of human neoplastic cell DNA by aphidicolin. Cancer Res.

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