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GnRH-III[8Lys(Dau=Aoa-Lys(Dau=Aoa))]
- Development stage
- Preclinical
- Lead developer
- Eötvös Loránd University
- Modality
- Peptide-Drug Conjugates → Peptide Conjugates → Peptides
- Administration
- Intravenous
01
Overview
GnRH-III[8Lys(Dau=Aoa-Lys(Dau=Aoa))] is a synthetic peptide-drug conjugate based on the decapeptide **GnRH-III** (a gonadotropin-releasing hormone analogue of sea lamprey origin) chemically modified at the 8th lysine residue with a side chain containing two molecules of **daunorubicin** (an anthracycline chemotherapeutic agent) covalently linked via aminooxyacetyl (Aoa) moieties through oxime bonds. This conjugate is designed as a targeted anticancer drug delivery system that leverages the high expression of GnRH receptors on certain tumor cells to achieve selective cytostatic and cytotoxic action. Upon receptor-mediated internalization, the conjugate is degraded in lysosomes to release drug-containing metabolites that bind to DNA and cause cytostatic/cytotoxic effects. It has shown antitumor activity in vitro (cell lines) and in vivo (mouse xenografts) against GnRH receptor–positive cancers, including breast and colon cancer. The conjugate improves the plasma stability and increases the cellular uptake compared to unmodified daunorubicin and serves as a platform for receptor-targeted therapy[2][3][8].
- Other names
- GnRH-III-dual-dauorubicin conjugateGnRH-III[8Lys(Dau=Aoa-Lys(Dau=Aoa))]
02
Targets
DNAGnRHR (Gonadotropin-releasing hormone receptor)
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