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termsTerm

Tetrapeptide GGFG (maleimide-GGFG-aminomethyl)

aka tetrapeptide linker, GGFG-DXd

The GGFG tetrapeptide is the four-amino-acid tether in Enhertu and Dato-DXd, cut by enzymes inside the cancer cell and very stable in blood.

The glycine-glycine-phenylalanine-glycine tetrapeptide is cleaved by lysosomal cathepsins, releasing DXd through a self-immolative aminomethylene spacer. Its stability in circulation allows a drug-to-antibody ratio of eight with acceptable off-target exposure, a combination that earlier linkers could not deliver.

Category
ADC chemistry

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