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Antineoplastic and immunomodulating drugs
Aldoxorubicin
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    Aldoxorubicin

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    Aldoxorubicin
    Aldoxorubicin.svg
    Identifiers
    • N-[[1-[(2S,4S)-4-[(2R,4S,5S,6S)-4-Amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]-2-hydroxyethylidene]amino]-6-(2,5-dioxopyrrol-1-yl)hexanamide
    CAS Number
    PubChem CID
    ChemSpider
    UNII
    KEGG
    ECHA InfoCard 100.244.879
    Chemical and physical data
    Formula C37H42N4O13
    Molar mass 750.758 g·mol−1
    3D model (JSmol)
    • C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](CC3=C(C4=C(C(=C23)O)C(=O)C5=C(C4=O)C=CC=C5OC)O)(C(=NNC(=O)CCCCCN6C(=O)C=CC6=O)CO)O)N)O
    • InChI=1S/C37H42N4O13/c1-17-32(46)20(38)13-27(53-17)54-22-15-37(51,23(16-42)39-40-24(43)9-4-3-5-12-41-25(44)10-11-26(41)45)14-19-29(22)36(50)31-30(34(19)48)33(47)18-7-6-8-21(52-2)28(18)35(31)49/h6-8,10-11,17,20,22,27,32,42,46,48,50-51H,3-5,9,12-16,38H2,1-2H3,(H,40,43)/t17-,20-,22-,27-,32+,37-/m0/s1
    • Key:OBMJQRLIQQTJLR-FRTGXRTISA-N

    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:

    1. After administration, aldoxorubicin rapidly binds endogenous circulating albumin through the EMCH linker.
    2. Circulating albumin preferentially accumulates in tumors, bypassing uptake by other non-specific sites including heart, bone marrow and gastrointestinal tract.
    3. Once albumin-bound aldoxorubicin reaches the tumor, the acidic environment of the tumor causes cleavage of the acid sensitive linker.
    4. 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:

    1. Second-line therapy for patients with glioblastoma
    2. Treatment of HIV-positive patients with Kaposi's sarcoma
    3. Combination therapy of ifosfamide and aldoxorubicin for treatment of metastatic or locally advanced sarcoma
    4. Comparison of aldoxorubicin to the gold-standard treatment, topotecan, for metastatic small cell lung cancer
    5. Treatment of advanced or metastatic pancreatic ductal adenocarcinoma
    6. Comparison of aldoxorubicin and doxorubicin for patients with metastatic or locally advanced carcinoma

    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. In November 2016, CytRx announced that preliminary results had been positive.

    Further reading


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