Aldoxorubicin
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| ECHA InfoCard | 100.244.879 |
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| Formula | C37H42N4O13 |
| Molar mass | 750.758 g·mol−1 |
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Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate in development by CytRx. Specifically, it is the (6-maleimidocaproyl) hydrazone of doxorubicin. Essentially, this chemical name describes doxorubicin attached to an acid-sensitive linker (N-ε-maleimidocaproic acid hydrazide, or EMCH).
The proposed mechanism of action is as follows:
- After administration, aldoxorubicin rapidly binds endogenous circulating albumin through the EMCH linker.
- Circulating albumin preferentially accumulates in tumors, bypassing uptake by other non-specific sites including heart, bone marrow and gastrointestinal tract.
- Once albumin-bound aldoxorubicin reaches the tumor, the acidic environment of the tumor causes cleavage of the acid sensitive linker.
- Free doxorubicin is released at the site of the tumor.
Clinical trials and FDA approvals
Aldoxorubicin was used in clinical trials to treat various forms of cancer, particularly soft-tissue sarcomas. Results from the sole phase III trial of Aldoxorubicin were considered disappointing as they did not meet their primary endpoint.[1] As of May 2025, aldoxorubicin has not been approved by the FDA for use in treating cancer.
References
- ^ Staff GE (2016-07-12). "CytRx's Aldoxorubicin Disappoints in Phase III Trial". GEN - Genetic Engineering and Biotechnology News. Retrieved 2025-05-20.
Further reading
- Kratz F, Azab S, Zeisig R, Fichtner I, Warnecke A (January 2013). "Evaluation of combination therapy schedules of doxorubicin and an acid-sensitive albumin-binding prodrug of doxorubicin in the MIA PaCa-2 pancreatic xenograft model". International Journal of Pharmaceutics. 441 (1–2): 499–506. doi:10.1016/j.ijpharm.2012.11.003. PMID 23149257.
- Walker L, Perkins E, Kratz F, Raucher D (October 2012). "Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative". International Journal of Pharmaceutics. 436 (1–2): 825–32. doi:10.1016/j.ijpharm.2012.07.043. PMC 3465682. PMID 22850291.
- Kratz F, Warnecke A (December 2012). "Finding the optimal balance: challenges of improving conventional cancer chemotherapy using suitable combinations with nano-sized drug delivery systems". Journal of Controlled Release. 164 (2): 221–35. doi:10.1016/j.jconrel.2012.05.045. PMID 22705248.
- Sanchez E, Li M, Wang C, Nichols CM, Li J, Chen H, Berenson JR (July 2012). "Anti-myeloma effects of the novel anthracycline derivative INNO-206". Clinical Cancer Research. 18 (14): 3856–67. doi:10.1158/1078-0432.CCR-11-3130. PMID 22619306. S2CID 7467600.