Global InformationZoptarelin doxorubicin information
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| Other names | AEZS-108; AN-152 |
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| ECHA InfoCard | 100.244.989 |
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| Formula | C91H117N19O26 |
| Molar mass | 1893.044 g·mol−1 |
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Zoptarelin doxorubicin (developmental code names AEZS-108, AN-152) consists of doxorubicin linked to a small peptide agonist to the luteinizing hormone-releasing hormone (LHRH) receptor.[1] It has been developed as a potential treatment for a number of human cancers. The LHRH receptor is aberrantly present on the cell surface of approximately 80% of endometrial and ovarian cancers, 86% of prostate cancers and about 50% of breast cancers. Whereas in normal tissues, expression of this receptor is mainly confined to the pituitary gland, reproductive organs and hematopoietic stem cells. To a lesser extent the LHRH receptor is also found on the surface of bladder, colorectal, and pancreatic cancers, sarcomas, lymphomas, melanomas, and renal cell carcinomas.[2]
The proposed method of action is that upon administration zoptarelin doxorubicin binds to the LHRH receptor and is subsequently internalized, concentrating the toxic doxorubicin within cancer cells and the small subset of normal tissues, as opposed to the completely systemic distribution observed with untargeted chemotherapeutics. The specific targeting of the doxorubicin to LHRH receptor bearing cells is also proposed to reduce the cardiotoxicity observed in the administration of unconjugated doxorubicin.
Zoptarelin doxorubicin was invented by Andrew V. Schally while at the Tulane University School of Medicine, New Orleans and subsequently at the Sylvester Comprehensive Cancer Center, University of Miami. It has been subsequently developed by AEterna Zentaris Inc. In June 2016, Aeterna stated that it plans to submit an NDA to the FDA by mid 2017.[3] Zoptarelin doxorubicin was discontinued for all indications under development in May 2017.[4]
The U.S. Food and Drug Administration (FDA) has granted it orphan drug status for ovarian cancer and endometrial cancer.
- ^ Rékási Z, Szöke B, Nagy A, Groot K, Rékási ES, Schally AV (May 1993). "Effect of luteinizing hormone-releasing hormone analogs containing cytotoxic radicals on the function of rat pituitary cells: tests in a long term superfusion system". Endocrinology. 132 (5): 1991–2000. doi:10.1210/endo.132.5.8477650. PMID 8477650.
- ^ Engel J, Emons G, Pinski J, Schally AV (June 2012). "AEZS-108 : a targeted cytotoxic analog of LHRH for the treatment of cancers positive for LHRH receptors". Expert Opinion on Investigational Drugs. 21 (6): 891–9. doi:10.1517/13543784.2012.685128. PMID 22577891. S2CID 37548203.
- ^ "Aeterna Zentaris Reconfirms Commitment to LHRH-receptor Targeting Zoptrex™ During 2016 ASCO Annual Meeting Pivotal Phase III Trial for Endometrial Cancer Expected to be Completed in Q3 2016". Aeterna Zentaris. 6 June 2016. Archived from the original on 4 February 2017.
- ^ "Zoptarelin doxorubicin". Adis Insight. Springer Nature Switzerland AG.