ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Mono-amino acid linkers enable highly potent small molecule-drug conjugates by conditional release.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. 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.
- Amanitin-Based Fc-Small Molecule-Drug Conjugates with Noncleavable Linker: A Novel Therapeutic Strategy for Prostate Cancer Targeted Therapy.Molecular cancer therapeutics · 2026Article
- A Review on the Stability Challenges of Advanced Biologic Therapeutics.Pharmaceutics · 2025Review
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Authors and funding
4 authors.
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Abstract
The endosome cleavable linkers have been widely employed by antibody-drug conjugates and small molecule-drug conjugates (SMDCs) to control the accurate release of payloads. An effective linker should provide stability in systemic circulation but efficient payload release at its targeted tumor sites. This conflicting requirement always leads to linker design with increasing structural complexity. Balance of the effectiveness and structural complexity presents a linker design challenge. Here, we explored the possibility of mono-amino acid as so far the simplest cleavable linker (X-linker) for SMDC-based auristatin delivery. Within a diverse set of X-linkers, the SMDCs differed widely in bioactivity, with one (Asn-linker) having significantly improved potency (IC
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