{"entity":{"id":"ggfg","kind":"term","name":"Tetrapeptide GGFG (maleimide-GGFG-aminomethyl)","aka":["tetrapeptide linker","GGFG-DXd"],"tldr":"The GGFG tetrapeptide (glycine-glycine-phenylalanine-glycine) is the tether between antibody and payload in Enhertu and Dato-DXd. Lysosomal cathepsins cut it inside the cancer cell, and it holds in circulation well enough to allow eight payloads per antibody, a load earlier linkers could not carry safely.","summary":"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.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Trastuzumab_deruxtecan","links":[{"label":"DS-8201a with GGFG-DXd linker-payload (Ogitani et al., Clin Cancer Res 2016)","url":"https://doi.org/10.1158/1078-0432.CCR-15-2822"}],"tags":[],"related":["dxd"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-deruxtecan","datopotamab-deruxtecan","patritumab-deruxtecan","ifinatamab-deruxtecan","raludotatug-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["linker"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ogitani-clin-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},"route":"/terms/ggfg/","neighbours":{"term":[{"id":"dxd","kind":"term","name":"DXd","route":"/terms/dxd/"},{"id":"linker","kind":"term","name":"Linker (ADC)","route":"/terms/linker/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"drug":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"ifinatamab-deruxtecan","kind":"drug","name":"Ifinatamab deruxtecan","route":"/drugs/ifinatamab-deruxtecan/"},{"id":"patritumab-deruxtecan","kind":"drug","name":"Patritumab deruxtecan","route":"/drugs/patritumab-deruxtecan/"},{"id":"raludotatug-deruxtecan","kind":"drug","name":"Raludotatug deruxtecan","route":"/drugs/raludotatug-deruxtecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"paper":[{"id":"paper-ogitani-clin-cancer-res","kind":"paper","name":"DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1","route":"/key-papers/paper-ogitani-clin-cancer-res/"}]}}