ArticleMolecules (Basel, Switzerland)2025
Design, Synthesis, and Evaluation of Camptothecin-Based Antibody-Drug Conjugates with High Hydrophilicity and Structural Stability.
Article in Molecules (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Engineering the Future of ADCs in Non-Small Cell Lung Cancer.Oncology research · 2026Review
- Graft Polymers Derived from Pharmaceutically Active Choline-Based Ionic Liquid Monomers: Dual Incorporation of Ampicillin and Cloxacillin.International journal of molecular sciences · 2025Article
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4 authors.
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Abstract
In this study, we constructed a linear antibody-drug conjugate (ADC), 7300-LP1003, by coupling the camptothecin derivative 095 to a linker through an ether bond. In vitro enzyme experiments indicated that LP1003 releases 095 through the action of tissue cathepsin B. Therefore, we introduced lysine pairs with different water-soluble substituents to further modify the linker and synthesized side-chain ADCs 7300-LP3004 and 7300-LP2004, modified by polysarcosine and polyethylene glycol, respectively. In vitro experiments showed that, after incubation at 55 °C in phosphate-buffered saline for 48 h, 7300-LP3004 aggregation was 45.24%, which was significantly lower than that of 7300-LP1003 (77.14%). Cell cytotoxicity assays demonstrated that the side-chain ADCs, 7300-LP3004 and 7300-LP2004, exhibited significantly higher activity (IC50 values of 39.74 nM and 32.17 nM, respectively) compared to the linear ADC and 7300-Deruxtecan (IC50 of 186.5 nM and 124.5 nM, respectively). In the subcutaneous model of SHP-77 NOD scid gamma mice, when the ADC dose was 5 mg/kg, 7300-LP3004 showed the highest tumor inhibition rate with a tumor growth inhibition (TGI) of 106.09%, which was superior to that of the positive control 7300-Deruxtecan, which had a TGI of 103.95%. In conclusion, 7300-LP3004 demonstrated strong antitumor activity and high physicochemical stability, highlighting the need for further research and development of ADC drugs.
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