Aldoxorubicin (INNO-206)

Alias: EMCH-doxorubicin; MC-DOXHZN hydrochloride; INNO 206; INNO-206 HCl; DOXO-EMCH; EMCH-Doxo; INNO206; INNO-206; Aldoxorubicin

Cat No.:V4150 Purity: ≥98%

COA Product Data Instructions for use SDS

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.

Aldoxorubicin (INNO-206) Chemical Structure CAS No.: 1361644-26-9
Product category: Topoisomerase

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Aldoxorubicin (INNO-206):

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

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Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

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Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

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.

Biological Activity I Assay Protocols (From Reference)

Targets	Daunorubicins/Doxorubicins; Topoisomerase II
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].
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].
References	[1]. Anti-Myeloma Effects of the Novel Anthracycline Derivative INNO-206. Clin Cancer Res.2012 18; 3856. [2]. INNO-206 (DOXO-EMCH), an Albumin-Binding Prodrug of Doxorubicin Under Development for Phase II Studies. Current Bioactive Compounds, 2011, 7(1): 33-38(6) [3]. INNO-206, the (6-maleimidocaproyl hydrazone derivative of doxorubicin), shows superior antitumor efficacy compared to doxorubicin in different tumor xenograft models and in an orthotopic pancreas carcinoma model. Invest New Drugs. 2010 F. [4]. Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative. Int J Pharm. 2012 Oct 15;436(1-2):825-32.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C37H42N4O13
Molecular Weight	750.748
Exact Mass	750.27
Elemental Analysis	C, 59.19; H, 5.64; N, 7.46; O, 27.70
CAS #	1361644-26-9
Related CAS #	MC-DOXHZN hydrochloride;480998-12-7;MC-DOXHZN;151038-96-9;Aldoxorubicin hydrochloride;1361563-03-2
Appearance	Solid powder
SMILES	C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(/C(=N/NC(=O)CCCCCN6C(=O)C=CC6=O)/CO)O)N)O
InChi Key	OBMJQRLIQQTJLR-USGQOSEYSA-N
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
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
Synonyms	EMCH-doxorubicin; MC-DOXHZN hydrochloride; INNO 206; INNO-206 HCl; DOXO-EMCH; EMCH-Doxo; INNO206; INNO-206; Aldoxorubicin
HS Tariff Code	2934.99.9001
Storage	Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)	DMSO: ≥ 50 mg/mL (~66.6 mM)
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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: ≥ 50 mg/mL (~66.6 mM)

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.
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 corn oil and mix evenly.

(Please use freshly prepared in vivo formulations for optimal results.)

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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

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Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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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.

Note： (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.

Clinical Trial Information

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

Biological Data

Chemical structure of 1 (6-maleimidocaproyl)hydrazone derivative of doxorubicin, DOXO-EMCH (re-named INNO-206) and 2 (6-maleimidocaproyl)amide derivative of doxorubicin, EMC-DOXO. Int J Pharm . 2012 Oct 15;436(1-2):825-32.

pH- and concentration-dependent inhibition of the viability of multiple myeloma cell lines after exposure to INNO-206 and doxorubicin. Clin Cancer Res (2012) 18 (14): 3856–3867.
Concentration- and pH-dependent inhibition of FB development after treatment with INNO-206. Clin Cancer Res (2012) 18 (14): 3856–3867.
Anti–multiple myeloma effects of INNO-206 in vivo using the LAGκ-1A xenograft model. Clin Cancer Res (2012) 18 (14): 3856–3867.
Anti–multiple myeloma effects of INNO-206 at 1.8 mg/kg 3 times weekly or 5.4 mg/kg once weekly, using the LAGκ-2 xenograft model. Clin Cancer Res (2012) 18 (14): 3856–3867.