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GnRH-III[4Lys(Ac),8Lys(Dau=Aoa)]
- Development stage
- Preclinical
- Lead developer
- Eötvös Loránd University
- Modality
- Peptide-Drug Conjugates → Peptide Conjugates → Peptides
- Administration
- Intravenous, Subcutaneous
01
Overview
GnRH-III[4Lys(Ac),8Lys(Dau=Aoa)] is a research-stage peptide-drug conjugate (PDC) designed for targeted cancer therapy. It utilizes a modified sea lamprey gonadotropin-releasing hormone-III (GnRH-III) peptide as a targeting moiety to deliver the cytotoxic anthracycline daunorubicin (Dau) specifically to cancer cells overexpressing GnRH receptors (GnRHR). The conjugate features an acetyl group at the lysine in position 4 and is linked to daunorubicin at the lysine in position 8 via an aminooxyacetyl (Aoa) linker, forming a stable oxime bond. Upon binding to GnRHR and subsequent internalization, the conjugate releases the daunorubicin payload, which acts as a DNA intercalator and topoisomerase II inhibitor. This mechanism leads to G2/M phase cell cycle arrest and apoptosis. In vivo studies in orthotopic murine colon carcinoma models have demonstrated significant tumor growth inhibition compared to free daunorubicin, highlighting its potential for reducing systemic toxicity while maintaining antitumor efficacy.
- Other names
- GnRH-III-daunorubicin conjugatedaunorubicin-GnRH-III bioconjugateGnRH-III-Dau conjugate
02
Targets
DNATOP2A (DNA topoisomerase II)GnRHR (Gonadotropin-releasing hormone receptor)
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