Английская Википедия:Aldoxorubicin
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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
Five phase I trials for safety characterization have been completed. Several phase II and III trials are underway.
Phase II
As of January 2017, there are 6 phase II clinical trials in progress:
- Second-line therapy for patients with glioblastoma[1]
- Treatment of HIV-positive patients with Kaposi's sarcoma[2]
- Combination therapy of ifosfamide and aldoxorubicin for treatment of metastatic or locally advanced sarcoma[3]
- Comparison of aldoxorubicin to the gold-standard treatment, topotecan, for metastatic small cell lung cancer[4]
- Treatment of advanced or metastatic pancreatic ductal adenocarcinoma[5]
- Comparison of aldoxorubicin and doxorubicin for patients with metastatic or locally advanced carcinoma[6]
Phase III
A phase III trial for patients with relapsed soft tissue sarcoma comparing aldoxorubicin with several other chemotherapeutics is expected to complete in 2018.[7] In November 2016, CytRx announced that preliminary results had been positive.[8]
References
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Further reading
