Cytotoxic activity and cell specificity of a novel LHRH peptide drug conjugate, D-Cys6-LHRH vedotin, against ovarian cancer cell lines

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Cytotoxic activity and cell specificity of a novel LHRH peptide drug conjugate, D-Cys6-LHRH vedotin, against ovarian cancer cell lines
Title:
Cytotoxic activity and cell specificity of a novel LHRH peptide drug conjugate, D-Cys6-LHRH vedotin, against ovarian cancer cell lines
Journal Title:
Chemical Biology & Drug Design
Keywords:
Publication Date:
15 April 2024
Citation:
Vankadara, S., Ke, Z., Wang, S., Foo, S. Y., Gunaratne, J., Lee, M. A., Koh, X., & Chia, C. S. B. (2024). Cytotoxic activity and cell specificity of a novel LHRH peptide drug conjugate, D-Cys6-LHRH vedotin, against ovarian cancer cell lines. Chemical Biology & Drug Design, 103(4). Portico. https://doi.org/10.1111/cbdd.14516
Abstract:
AbstractOvarian cancer is the most deadly female gynaecological malignancy in developed countries and new treatments are urgently needed. The luteinising hormone releasing hormone (LHRH) peptide drug conjugate Zoptarelin doxorubicin is one such potential new drug modality that entered clinical trials for treating LHRH receptor‐positive gynaecological cancers. However, development stopped after disappointing Phase 3 results in 2017. We believe the lack of efficacy was due to linker instability and payload potency. In this work, we replaced its linker‐toxin with vedotin (MC‐VC‐PABC‐MMAE), yielding the novel peptide drug conjugate D‐Cys6‐LHRH vedotin. A GI50 and cell specificity comparison against cancerous and non‐cancerous ovarian cell lines showed significantly superior bioactivity and selectivity over Zoptarelin doxorubicin (GI50 4 vs. 453 nM) and other chemotherapeutic drugs used for treating ovarian cancers. Our results suggest D‐Cys6‐LHRH vedotin can potentially be used as a treatment for ovarian cancer.
License type:
Publisher Copyright
Funding Info:
This research is supported by core funding from: Experimental Drug Development Centre (EDDC)
Grant Reference no. : N. A.
Description:
This is the peer reviewed version of the following article: Vankadara, S., Ke, Z., Wang, S., Foo, S. Y., Gunaratne, J., Lee, M. A., Koh, X., & Chia, C. S. B. (2024). Cytotoxic activity and cell specificity of a novel LHRH peptide drug conjugate, D-Cys6-LHRH vedotin, against ovarian cancer cell lines. Chemical Biology & Drug Design, 103(4). Portico. https://doi.org/10.1111/cbdd.14516, which has been published in final form at doi.org/10.1111/cbdd.14516. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited
ISSN:
1747-0277
1747-0285
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