ArticleMolecular cancer therapeutics2024
Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates.
Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Article
- Enhanced subcutaneous delivery of antibody-drug conjugates with recombinant human hyaluronidase PH20: pharmacokinetics and tolerability in minipigs.Drug delivery and translational research · 2026Article
- Exatecan Payload-Based Antibody-Drug Conjugates with a Short Hydrophilic Cleavable Linker.ACS medicinal chemistry letters · 2026Article
- Antibody-drug conjugates for infectious and neglected tropical diseases: chemical design principles, target biology, and translational challenges.Frontiers in chemistry · 2026Review
- Antibody-Drug Conjugates in Breast Cancer: Navigating Innovations, Overcoming Resistance, and Shaping Future Therapies.Biomedicines · 2025Review
- T330M Substitution in the Sodium-Dependent Phosphate Transporter NaPi2b Abolishes the Efficacy of Monoclonal Antibodies Against MX35 Epitope.Antibodies (Basel, Switzerland) · 2025Article
- Camptothecin: a key building block in the design of anti-tumor agents.Future medicinal chemistry · 2025Article
- Emerging Claudin18.2-targeting Therapy for Systemic Treatment of Gastric Cancer: Seeking Nobility Amidst Danger.Anti-cancer agents in medicinal chemistry · 2025Review
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by the clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present the development of a novel camptothecin ZD06519 (FD1), which has been specifically designed for its application as an ADC payload. A panel of camptothecin analogs with different substituents at the C-7 and C-10 positions of the camptothecin core was prepared and tested in vitro. Selected compounds spanning a range of potency and hydrophilicity were elaborated into drug-linkers, conjugated to trastuzumab, and evaluated in vitro and in vivo. ZD06519 was selected on the basis of its favorable properties as a free molecule and as an antibody conjugate, which include moderate free payload potency (∼1 nmol/L), low hydrophobicity, strong bystander activity, robust plasma stability, and high-monomeric ADC content. When conjugated to different antibodies using a clinically validated MC-GGFG-based linker, ZD06519 demonstrated impressive efficacy in multiple cell line-derived xenograft models and noteworthy tolerability in healthy mice, rats, and non-human primates.
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