Abstract
Onrigen (also called laromustine, cloretazine, VNP4101M, 101M) a sulfonylhydrazine prodrug first synthesized in the Sartorelli laboratory, undergoes a base-catalyzed activation, generating two reactive electrophiles, one with chloroethylating activity and the other with carbamoylating activity. Assays in biochemical systems and intact cells showed that the chloroethylating species primarily alkylates DNA at the O-6 position of guanine, ultimately resulting in the formation of interstrand crosslinks with cytosine on the opposite strand.
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