(1S)-seco-CBI-DMAI-β-D-galactoside

(1S)-seco-CBI-DMAI-β-D-galactoside is a synthetic, enzyme-activatable prodrug designed for use in gene-directed enzyme prodrug therapy (GDEPT) and oncolytic virotherapy. The molecule consists of a seco-CBI (cyclopropabenzindolone) alkylating subunit and a DMAI (dimethylaminoindole) DNA-binding subunit, masked by a β-D-galactoside moiety. This masking renders the prodrug relatively non-toxic until it is selectively cleaved by the enzyme β-galactosidase (encoded by the lacZ gene). In therapeutic applications, such as those involving the oncolytic vaccinia virus strain GLV-1h68, the virus delivers the lacZ gene to tumor cells. Upon expression of β-galactosidase, the prodrug is converted into its active, highly potent DNA-alkylating form, which induces sequence-specific DNA damage in the minor groove and triggers the intrinsic apoptosis pathway specifically within the infected tumor microenvironment.

Other names

seco-CBI-DMAI-galbeta-galactosidase-activatable duocarmycin prodrug