Aldoxorubicin

{{Infobox drug

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| IUPAC_name = 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

| image = Aldoxorubicin.svg

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| CAS_number = 1361644-26-9

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = C28MV4IM0B

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| PubChem = 71300693

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| ChemSpiderID = 7986464

| KEGG = D10383

| C=37|H=42|N=4|O=13

| StdInChIKey= OBMJQRLIQQTJLR-FRTGXRTISA-N

| StdInChI=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

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Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate in development by CytRx. Specifically, it is the (6-maleimido caproyl) 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{{ClinicalTrialsGov|NCT02014844|Phase 2 Study to Investigate the Efficacy and Safety of Aldoxorubicin in Subjects With Glioblastoma}}
Treatment of HIV-positive patients with Kaposi's sarcoma{{ClinicalTrialsGov|NCT02029430|A Study to Investigate ALDOXORUBICIN in HIV-infected Subjects With Kaposi's Sarcoma}}
Combination therapy of ifosfamide and aldoxorubicin for treatment of metastatic or locally advanced sarcoma{{ClinicalTrialsGov|NCT02235701|Study to Investigate the Safety and Activity of Aldoxorubicin Plus Ifosfamide/Mesna in Subjects With Metastatic Soft Tissue Sarcoma}}
Comparison of aldoxorubicin to the gold-standard treatment, topotecan, for metastatic small cell lung cancer{{ClinicalTrialsGov|NCT02200757|Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer}}
Treatment of advanced or metastatic pancreatic ductal adenocarcinoma{{ClinicalTrialsGov|NCT01580397|Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of INNO-206 in Advanced Pancreatic Cancer}}
Comparison of aldoxorubicin and doxorubicin for patients with metastatic or locally advanced carcinoma{{ClinicalTrialsGov|NCT01514188|Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma}}

= Phase III =

{{Update|reason=The trial completion date was due in 2018, but the current status or results have not been updated. There may be newer developments.|date=January 2025}}

A phase III trial for patients with relapsed soft tissue sarcoma comparing aldoxorubicin with several other chemotherapeutics is expected to complete in 2018.{{ClinicalTrialsGov|NCT02049905|Phase 3 Study to Treat Patients With Soft Tissue Sarcomas}} In November 2016, CytRx announced that preliminary results had been positive.{{cite web | title = CytRx (CYTR) Announces Statistically Significant Data from Aldoxorubicin Phase 3 in r/r STS | date = 29 November 2016 | url = http://www.streetinsider.com/Conference+Calls/CytRx+(CYTR)+Announces+Statistically+Significant+Data+from+Aldoxorubicin+Phase+3+in+rr+STS/12289769.html }}

Aldoxorubicin

Clinical trials

= Phase II =

= Phase III =

References

Further reading