# Peptide-drug & small-molecule-drug conjugates

Source: https://onco.cc/technologies/peptide-drug-conjugate/  
OnCo record `peptide-drug-conjugate` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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 Examples include melflufen (Pepaxto, withdrawn in the US), lutetium radioligands (technically peptide-radionuclide conjugates), and clinical-stage PDCs such as BT8009 zelenectide pevedotin, a Nectin-4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.

## Fields

- Kind: Technology
- Status: approved
- Last checked: 2026-09-04
- 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

## Sources

- Cooper et al., Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (Chemical Society Reviews 2021): https://doi.org/10.1039/D0CS00556H

## Connected records

- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [De novo designed protein binders](https://onco.cc/technologies/de-novo-protein-design/)
- targets: [Nectin-4](https://onco.cc/targets/nectin4/)
- key papers: [Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (PDCs)](https://onco.cc/key-papers/paper-cooper-chem-soc-rev/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/)
- drugs: [Melphalan flufenamide](https://onco.cc/drugs/melflufen/), [Rusfertide](https://onco.cc/drugs/rusfertide/), [Zelenectide pevedotin](https://onco.cc/drugs/zelenectide-pevedotin/)
- companies: [Aeterna Zentaris](https://onco.cc/companies/aeterna-zentaris/), [Bicycle Therapeutics](https://onco.cc/companies/bicycle-therapeutics/)
- roadmaps: [ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs](https://onco.cc/roadmaps/adc-generations/), [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/)
- terms: [Small molecule drug](https://onco.cc/terms/small-molecule/)
- institutions: [Purdue Institute for Cancer Research](https://onco.cc/institutions/purdue-cancer-research/), [Sanford Burnham Prebys Medical Discovery Institute](https://onco.cc/institutions/sanford-burnham-prebys/)
- trials: [A Study of Rusfertide in Japanese Adults With Polycythemia Vera](https://onco.cc/trials/nct07648030/), [Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Malignancies](https://onco.cc/trials/nct04561362/), [Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)](https://onco.cc/trials/nct06225596/), [Study of Zelenectide Pevedotin in Participants With Advanced Breast Cancer](https://onco.cc/trials/nct06840483/), [Study to Evaluate the Long-term Safety of Rusfertide (PTG-300) in Subjects With Polycythemia Vera](https://onco.cc/trials/nct06033586/), [VERIFY](https://onco.cc/trials/verify/), [Zelenectide Pevedotin in NECTIN4 Amplified Advanced or Metastatic Non-small Cell Lung Cancer](https://onco.cc/trials/nct06933329/)

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