| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
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Purity: ≥98%
Aldoxorubicin (MC-DOXHZN; INNO206, Doxo-EMCH, INNO-206) is an albumin-binding prodrug of doxorubicin, which is a DNA topoisomerase II inhibitor and anthracycline antibiotic anticancer drug. The EMCH linker facilitates the binding of aldoxorubicin to endogenous circulating albumin. The gastrointestinal tract, bone marrow, heart, and other non-specific sites are not where circulating albumin is preferentially accumulated; instead, it accumulates in tumors. Following its delivery to the tumor, albumin-bound aldoxorubicin is released at the tumor site when the acidic environment of the tumor causes the acid-sensitive linker to cleave.
| Targets |
Daunorubicins/Doxorubicins; Topoisomerase II
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| ln Vitro |
Aldoxorubicin (INNO-206) (0.27 to 2.16 μM) inhibits the formation of blood vessels and decreases the growth of multiple myeloma cells in a pH-dependent fashion[1].
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| ln Vivo |
Aldoxorubicin (INNO-206) (10.8 mg/kg, i.v.) is well tolerated; 90% of mice with the LAGκ-1A tumor survive until the study's conclusion[1]. It also exhibits significantly smaller tumor volumes and IgG levels on day 28. Phase I studies have shown that aldoxorubicin (INNO-206) can cause tumor regressions in sarcoma, small cell lung cancer, and breast cancer while maintaining a good safety profile at doses up to 260 mg/mL doxorubicin equivalents[2]. In models of breast carcinoma xenografts and murine renal cell carcinoma, aldoxorubicin (INNO-206) exhibits better efficacy than doxorubicin[3].
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| Cell Assay |
Cell viability assay[1]
Cells were seeded at 1 × 105 cells/100 μL/well in 96-well plates in RPMI-1640 media with FBS for 24 hours before treatment. Cells were cultured in the presence of medium, INNO-206 or doxorubicin for 48 hours. Next, cell viability was quantified using the CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay (Promega). Each well was treated with MTS for 1 to 4 hours, after which absorbance at 490 nm was recorded using a 96-well plate reader. The quantity of formazan product as measured is directly proportional to the number of living cells. Data graphed are means ± SEM using 3 replicates per data point. The anti–multiple myeloma effect of INNO-206 at different pH levels on multiple myeloma cell proliferation using multiple myeloma cell lines with the MTS assay and antiangiogenic activity using the chorioallantoic membrane/feather bud assay were determined. The anti–multiple myeloma effects and toxicity of INNO-206 were also compared with conventional doxorubicin and PEGylated liposomal doxorubicin (PLD) alone, and in combination with bortezomib, using our multiple myeloma xenograft models[1]. |
| Animal Protocol |
INNO-206 stock solutions (5.4 mg/mL) were prepared using 50% ethanol and 50% water and further diluted in sterile water. [1]
For the LAGκ-1A experiment, INNO-206 was administered to SCID mice at 10.8 mg/kg (doxorubicin equivalent dose of 8.0 mg/kg) once weekly. Mice were treated with conventional doxorubicin at 4.0 and 8.0 mg/kg once weekly. For the LAGκ-2 experiment, INNO-206 was administered once weekly (W) at doses of 2.7 and 5.4 mg/kg, or on 3 consecutive days (W-F) weekly at doses of 0.9 and 1.8 mg/kg. Bortezomib was administered twice weekly (W, F) at a dose of 0.5 mg/kg. Doxorubicin was administered to SCID mice at 2, 4, and 8 mg/kg, and PLD was administered to SCID mice at 2 mg/kg once weekly. Each drug was administered i.v. in a volume of 100 μL.[1] The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (INNO-206) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that is being assessed clinically. The prodrug binds rapidly to circulating serum albumin and releases doxorubicin selectively at the tumor site. This novel mechanism may provide enhanced antitumor activity of doxorubicin while improving the overall toxicity profile. Preclinically, INNO-206 has shown superior activity over doxorubicin in a murine renal cell carcinoma model and in breast carcinoma xenograft models. In this work, we compared the antitumor activity of INNO-206 and doxorubicin at their respective maximum tolerated doses in three additional xenograft models (breast carcinoma 3366, ovarian carcinoma A2780, and small cell lung cancer H209) as well as in an orthotopic pancreas carcinoma model (AsPC-1). INNO-206 showed more potent antitumor efficacy than free doxorubicin in all tumor models and is thus a promising clinical candidate for treating a broad range of solid tumors[3]. |
| References |
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| Additional Infomation |
Aldoxorubicin, an antineoplastic agents, is an albumin-binding prodrug of doxorubicin.
Aldoxorubicin is a 6-maleimidocaproyl hydrazone derivative prodrug of the anthracycline antibiotic doxorubicin (DOXO-EMCH) with antineoplastic activity. Following intravenous administration, aldoxorubicin binds selectively to the cysteine-34 position of albumin via its maleimide moiety. Doxorubicin is released from the albumin carrier after cleavage of the acid-sensitive hydrazone linker within the acidic environment of tumors and, once located intracellularly, intercalates DNA, inhibits DNA synthesis, and induces apoptosis. Albumin tends to accumulate in solid tumors as a result of high metabolic turnover, rapid angiogenesis, hypervasculature, and impaired lymphatic drainage. Because of passive accumulation within tumors, this agent may improve the therapeutic effects of doxorubicin while minimizing systemic toxicity. Drug Indication Investigated for use/treatment in solid tumors. Mechanism of Action INNO-206 is the (6-Maleimidocaproyl) hydrazone of doxorubicin. INNO-206 is a prodrug of doxorubicin that binds endogenous albumin after administration. The bound doxorubicin is released in the acidic environment of the tumor cell through cleavage of an acid sensitive linker. In preclinical models, INNO-206 was superior to doxorubicin with regard to antitumor efficacy and toxicity. |
| Molecular Formula |
C37H42N4O13
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| Molecular Weight |
750.748
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| Exact Mass |
750.274
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| Elemental Analysis |
C, 59.19; H, 5.64; N, 7.46; O, 27.70
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| CAS # |
1361644-26-9
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| Related CAS # |
MC-DOXHZN hydrochloride;480998-12-7;MC-DOXHZN;151038-96-9;Aldoxorubicin hydrochloride;1361563-03-2
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| PubChem CID |
9810709
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| Appearance |
Purple to purplish red solid powder
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| Density |
1.6±0.1 g/cm3
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| Index of Refraction |
1.708
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| LogP |
3.08
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
54
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| Complexity |
1510
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| Defined Atom Stereocenter Count |
6
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| SMILES |
[H][C@@]1(O[C@H]2C[C@@](/C(CO)=N/NC(CCCCCN3C(C=CC3=O)=O)=O)(O)CC(C2=C4O)=C(O)C5=C4C(C6=C(OC)C=CC=C6C5=O)=O)O[C@@H](C)[C@@H](O)[C@@H](N)C1
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| InChi Key |
OBMJQRLIQQTJLR-USGQOSEYSA-N
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| InChi Code |
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)/b39-23+/t17-,20-,22-,27-,32+,37-/m0/s1
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| Chemical Name |
N-[(E)-[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
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| Synonyms |
EMCH-doxorubicin; MC-DOXHZN hydrochloride; INNO 206; INNO-206 HCl; DOXO-EMCH; EMCH-Doxo; INNO206; INNO-206; Doxorubicin-EMCH; 151038-96-9; MC-Doxhzn; N-[(E)-[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; Aldoxorubicin
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (2). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| Shipping Condition |
Ship with dry ice
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| Solubility (In Vitro) |
DMSO: ≥ 50 mg/mL (~66.6 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3320 mL | 6.6600 mL | 13.3200 mL | |
| 5 mM | 0.2664 mL | 1.3320 mL | 2.6640 mL | |
| 10 mM | 0.1332 mL | 0.6660 mL | 1.3320 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03387085 | Active Recruiting |
Drug: Aldoxorubicin HCl Biological: N-803 |
Triple Negative Breast Cancer | ImmunityBio, Inc. | March 16, 2018 | Phase 1 Phase 2 |
| NCT03563157 | Active Recruiting |
Biological: ALT-803 Biological: ETBX-011 |
Colorectal Cancer Metastatic mCRC |
ImmunityBio, Inc. | May 25, 2018 | Phase 1 Phase 2 |
| NCT04390399 | Recruiting | Drug: Aldoxorubicin HCl Biological: PD-L1 t-haNK |
Pancreatic Cancer | ImmunityBio, Inc. | July 21, 2020 | Phase 2 |
| NCT02029430 | Completed | Drug: aldoxorubicin | AIDS HIV Positive |
ImmunityBio, Inc. | January 2014 | Phase 2 |
| NCT02014844 | Completed | Drug: aldoxorubicin | Glioblastoma | ImmunityBio, Inc. | March 2014 | Phase 2 |
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