MedKoo product information:

 AEZS-108

Description of AEZS-108: AEZS-108 (AN-152, or zoptarelin doxorubicin) is a targeted cytotoxic peptide conjugate which is a hybrid molecule composed of a synthetic peptide carrier and a well-known cytotoxic agent, doxorubicin. The design of this product allows for the specific binding and selective uptake of the cytotoxic conjugate by the LHRH receptor-positive tumors. The binding of conjugate molecule AEZS-108 to cancerous cells that express these receptors results in its accumulation in the malignant tissue. This binding is followed by internalization and retention of the cytotoxic drug, doxorubicin, in the cells. Therefore, since they target specific cells, cytotoxic conjugates are postulated to be more effective and have less side-effects than the respective non-conjugated/non-linked cytotoxic agents in inhibiting tumor growth. AEZS-108 is the first drug in a clinical study that targets the cytotoxic activity of doxorubicin specifically to LHRH-receptor expressing tumors. (source: http://www.aezsinc.com/en/page.php?p=31&prod=16).

Current developer:    AEterna-Zentaris

AEZS-108 (previously AN-152) consists of [D-Lys(6)] LHRH linked to doxorubicin. It is an experimental targeted therapy for various cancers (ovarian, endometrial, breast, bladder, prostate) that express LHRH receptor.

AEZS-108 is currently being developed by AEterna-Zentaris. The US FDA has granted it orphan drug status for ovarian cancer. Promising results have been reported from a phase II clinical trial for ovarian cancer. It is also in a phase II trial for endometrial cancer. A Phase I trial for bladder cancer using AEZS-108 is currently underway at the University of MIami using a synthetic form of LHRH developed by Dr. Andrew Schally, a Nobel Prize Laureate. Early results from this trial have shown promise. (Source: http://en.wikipedia.org/wiki/AEZS-108). 

Acordingto AEterna-Zentaris's website,  After having successfully completed the Phase 2 trials in ovarian and endometrial cancer, we expect to initiate a first pivotal trial in endometrial cancer during 2011. AEZS-108 has been granted orphan-drug designation by the FDA for ovarian cancer. Furthermore, AEZS-108 is being investigated in Phase 1/2 trials in prostate and bladder cancer. (source: http://www.aezsinc.com/en/page.php?p=31&prod=16).

1: Gründker C, Ernst J, Reutter MD, Ghadimi BM, Emons G. Effective targeted chemotherapy using AEZS-108 (AN-152) for LHRH receptor-positive pancreatic cancers. Oncol Rep. 2011 Sep;26(3):629-35. doi: 10.3892/or.2011.1340. Epub 2011 Jun 7. PubMed PMID: 21667032.

2: Emons G, Kaufmann M, Gorchev G, Tsekova V, Gründker C, Günthert AR, Hanker LC, Velikova M, Sindermann H, Engel J, Schally AV. Dose escalation and pharmacokinetic study of AEZS-108 (AN-152), an LHRH agonist linked to doxorubicin, in women with LHRH receptor-positive tumors. Gynecol Oncol. 2010 Dec;119(3):457-61. Epub 2010 Sep 9. PubMed PMID: 20828803.

3: Emons G, Sindermann H, Engel J, Schally AV, Gründker C. Luteinizing hormone-releasing hormone receptor-targeted chemotherapy using AN-152. Neuroendocrinology. 2009;90(1):15-8. Epub 2009 Jun 12. PubMed PMID: 19521066.

4: Engel JB, Keller G, Schally AV, Nagy A, Chism DD, Halmos G. Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone-releasing hormone analogues AN-152 and AN-207. Fertil Steril. 2005 Apr;83 Suppl 1:1125-33. PubMed PMID: 15831285.

5: Günthert AR, Gründker C, Bongertz T, Nagy A, Schally AV, Emons G. Induction of apoptosis by AN-152, a cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), in LHRH-R positive human breast cancer cells is independent of multidrug resistance-1 (MDR-1) system. Breast Cancer Res Treat. 2004 Oct;87(3):255-64. PubMed PMID: 15528968.

6: Günthert AR, Gründker C, Bongertz T, Schlott T, Nagy A, Schally AV, Emons G. Internalization of cytotoxic analog AN-152 of luteinizing hormone-releasing hormone induces apoptosis in human endometrial and ovarian cancer cell lines independent of multidrug resistance-1 (MDR-1) system. Am J Obstet Gynecol. 2004 Oct;191(4):1164-72. PubMed PMID: 15507937.

7: Letsch M, Schally AV, Szepeshazi K, Halmos G, Nagy A. Preclinical evaluation of targeted cytotoxic luteinizing hormone-releasing hormone analogue AN-152 in androgen-sensitive and insensitive prostate cancers. Clin Cancer Res. 2003 Oct 1;9(12):4505-13. PubMed PMID: 14555524.

8: Bajo AM, Schally AV, Halmos G, Nagy A. Targeted doxorubicin-containing luteinizing hormone-releasing hormone analogue AN-152 inhibits the growth of doxorubicin-resistant MX-1 human breast cancers. Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3742-8. PubMed PMID: 14506166.

9: Krebs LJ, Wang X, Nagy A, Schally AV, Prasad PN, Liebow C. Bombesin and epidermal growth factor potentiate the effect of cytotoxic LH-RH analog AN-152 in vitro. Int J Oncol. 2002 Dec;21(6):1325-9. PubMed PMID: 12429984.

10: Gründker C, Völker P, Griesinger F, Ramaswamy A, Nagy A, Schally AV, Emons G. Antitumor effects of the cytotoxic luteinizing hormone-releasing hormone analog AN-152 on human endometrial and ovarian cancers xenografted into nude mice. Am J Obstet Gynecol. 2002 Sep;187(3):528-37. PubMed PMID: 12237622.

11: Westphalen S, Kotulla G, Kaiser F, Krauss W, Werning G, Elsasser HP, Nagy A, Schulz KD, Grundker C, Schally AV, Emons G. Receptor mediated antiproliferative effects of the cytotoxic LHRH agonist AN-152 in human ovarian and endometrial cancer cell lines. Int J Oncol. 2000 Nov;17(5):1063-9. PubMed PMID: 11029513.

12: Nagy A, Plonowski A, Schally AV. Stability of cytotoxic luteinizing hormone-releasing hormone conjugate (AN-152) containing doxorubicin 14-O-hemiglutarate in mouse and human serum in vitro: implications for the design of preclinical studies. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):829-34. PubMed PMID: 10639165; PubMed Central PMCID: PMC15416.