{"entity":{"id":"peptide-drug-conjugate","kind":"technology","name":"Peptide-drug & small-molecule-drug conjugates","aka":[],"tldr":"Like an ADC but with a small targeting peptide instead of an antibody, so it penetrates tumours faster and is cheaper to make.","summary":"Peptide-drug conjugates replace the antibody of an ADC with a short or bicyclic peptide that binds the target, giving rapid tumour penetration and renal clearance, with a short half-life that reduces systemic exposure and cheaper synthesis. Examples include melflufen (Pepaxto, withdrawn in the US), lutetium radioligands (technically peptide-radionuclide conjugates), and clinical-stage PDCs such as BT8009 zelenectide pevedotin, a Nectin-4 Bicycle toxin conjugate, and CBX-12, an exatecan-SMDC. Bicycle's zelenectide pevedotin is in phase 2/3 in urothelial cancer. The same short half-life that limits toxicity also limits tumour exposure, and renal toxicity is a class concern. The simple version is an ADC with a small peptide as the address label, faster to penetrate tumours and cheaper to make.","status":"approved","asOf":"2026-09-04","links":[{"label":"Cooper et al., Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (Chemical Society Reviews 2021)","url":"https://doi.org/10.1039/D0CS00556H"}],"tags":[],"related":[],"cancers":[],"sections":["adcs"],"technologies":["adc"],"targets":["nectin4"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cooper-chem-soc-rev"],"journals":[],"dependsOn":[],"notes":[],"principle":"Short peptide or bicyclic peptide binds the target; short half-life reduces systemic exposure.","strengths":["Rapid penetration, renal clearance","Cheaper synthesis"],"limitations":["Short half-life limits tumour exposure","Renal toxicity"]},"route":"/technologies/peptide-drug-conjugate/","neighbours":{"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"de-novo-protein-design","kind":"technology","name":"De novo designed protein binders","route":"/technologies/de-novo-protein-design/"}],"target":[{"id":"nectin4","kind":"target","name":"Nectin-4","route":"/targets/nectin4/"}],"paper":[{"id":"paper-cooper-chem-soc-rev","kind":"paper","name":"Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (PDCs)","route":"/key-papers/paper-cooper-chem-soc-rev/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"}],"drug":[{"id":"melflufen","kind":"drug","name":"Melphalan flufenamide","route":"/drugs/melflufen/"},{"id":"rusfertide","kind":"drug","name":"Rusfertide","route":"/drugs/rusfertide/"},{"id":"zelenectide-pevedotin","kind":"drug","name":"Zelenectide pevedotin","route":"/drugs/zelenectide-pevedotin/"}],"company":[{"id":"aeterna-zentaris","kind":"company","name":"Aeterna Zentaris","route":"/companies/aeterna-zentaris/"},{"id":"bicycle-therapeutics","kind":"company","name":"Bicycle Therapeutics","route":"/companies/bicycle-therapeutics/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"},{"id":"drug-discovery-roadmap","kind":"roadmap","name":"Drug discovery roadmap: screening in mice → maps of dependency → designing in silico","route":"/roadmaps/drug-discovery-roadmap/"}],"term":[{"id":"small-molecule","kind":"term","name":"Small molecule drug","route":"/terms/small-molecule/"}],"institution":[{"id":"purdue-cancer-research","kind":"institution","name":"Purdue Institute for Cancer Research","route":"/institutions/purdue-cancer-research/"},{"id":"sanford-burnham-prebys","kind":"institution","name":"Sanford Burnham Prebys Medical Discovery Institute","route":"/institutions/sanford-burnham-prebys/"}],"trial":[{"id":"nct07648030","kind":"trial","name":"A Study of Rusfertide in Japanese Adults With Polycythemia Vera","route":"/trials/nct07648030/"},{"id":"nct04561362","kind":"trial","name":"Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Malignancies","route":"/trials/nct04561362/"},{"id":"nct06225596","kind":"trial","name":"Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)","route":"/trials/nct06225596/"},{"id":"nct06840483","kind":"trial","name":"Study of Zelenectide Pevedotin in Participants With Advanced Breast Cancer","route":"/trials/nct06840483/"},{"id":"nct06033586","kind":"trial","name":"Study to Evaluate the Long-term Safety of Rusfertide (PTG-300) in Subjects With Polycythemia Vera","route":"/trials/nct06033586/"},{"id":"verify","kind":"trial","name":"VERIFY","route":"/trials/verify/"},{"id":"nct06933329","kind":"trial","name":"Zelenectide Pevedotin in NECTIN4 Amplified Advanced or Metastatic Non-small Cell Lung Cancer","route":"/trials/nct06933329/"}]}}