INNO-206 - CAS 1361644-26-9

INNO-206 - CAS 1361644-26-9 Catalog number: BADC-00027

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INNO-206 (Aldoxorubicin) is the 6-maleimidocaproyl hydrazone derivative prodrug of the anthracycline antibiotic doxorubicin (DOXO-EMCH) with antineoplastic activity.

Category
ADCs Cytotoxin
Product Name
INNO-206
CAS
1361644-26-9
Catalog Number
BADC-00027
Molecular Formula
C37H42N4O13
Molecular Weight
750.75
Purity
>98%
INNO-206

Ordering Information

Catalog Number Size Price Quantity
BADC-00027 -- $-- Inquiry
Description
INNO-206 (Aldoxorubicin) is the 6-maleimidocaproyl hydrazone derivative prodrug of the anthracycline antibiotic doxorubicin (DOXO-EMCH) with antineoplastic activity.
Synonyms
Doxorubicin-hydrazone-caproyl-maleimide; Aldoxorubicin; 2,5-Dihydro-2,5-dioxo-1H-pyrrole-1-hexanoic acid (2E)-2-[1-[(2S,4S)-4-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-2-naphthacenyl]-2-hydroxyethylidene]hydrazide; 1H-Pyrrole-1-hexanoic acid, 2,5-dihydro-2,5-dioxo-, (2E)-2-[1-[(2S,4S)-4-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-2-naphthacenyl]-2-hydroxyethylidene]hydrazide; INNO 206; INNO206
IUPAC 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
Canonical SMILES
CC1C(C(CC(O1)OC2CC(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
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
InChIKey
OBMJQRLIQQTJLR-USGQOSEYSA-N
Density
1.60±0.1 g/cm3
Solubility
Soluble in DMSO
Index Of Refraction
1.708
LogP
3.08
PSA
271.33000
Appearance
Solid Power
Shelf Life
≥360 days if stored properly
Shipping
Room temperature, or blue ice upon request.
Storage
Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)
Pictograms
Health Hazard
Signal Word
Danger
In Vitro
Aldoxorubicin (INNO-206) inhibited blood vessel formation and reduced multiple myeloma cell growth in a pH-dependent fashion. INNO-206 alone produced marked anti-multiple myeloma effects in vivo at doses that doxorubicin was toxic, and the combination of INNO-206 plus bortezomib produced increased anti-multiple myeloma effects compared with either agent alone. In contrast, all mice receiving bortezomib with doxorubicin or PLD died.
In Vivo
INNO-206 inhibited blood vessel formation and reduced multiple myeloma cell growth in a pH-dependent fashion. INNO-206 alone produced marked anti-multiple myeloma effects in vivo at doses that doxorubicin was toxic, and the combination of INNO-206 plus bortezomib produced increased anti-multiple myeloma effects compared with either agent alone. In contrast, all mice receiving bortezomib with doxorubicin or PLD died.
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.
NCT NumberCondition Or DiseasePhaseStart DateSponsorStatus
NCT01580397Pancreatic Ductal AdenocarcinomaPhase 22013-06-28CytRxCompleted
NCT02014844GlioblastomaPhase 22017-01-06CytRxCompleted
NCT01706835Advanced Solid TumorsPhase 12014-12-17CytRxCompleted
NCT02235688Metastatic Solid TumorsPhase 12017-06-07CytRxCompleted
NCT01337505Malignant Solid TumourPhase 12013-02-13CytRxCompleted

INNO-206 is a novel prodrug of the potent cytotoxic agent monomethyl auristatin E (MMAE), designed for targeted cancer therapy. The compound is a part of the antibody-drug conjugate (ADC) strategy, where MMAE is conjugated to an antibody through a cleavable linker. INNO-206 uses the valine-citrulline (Vc) linker, which is specifically cleaved by enzymes inside cancer cells, allowing for the selective release of MMAE. This design enhances the specificity of drug delivery, reducing systemic toxicity and increasing the effectiveness of chemotherapy, making it a promising candidate for targeted cancer treatment.

The primary application of INNO-206 is in the treatment of various types of cancers, particularly those with overexpression of specific tumor-associated antigens. The ADC's antibody component is engineered to recognize and bind to these antigens, such as those found on the surface of cancer cells, enabling selective internalization and delivery of the potent MMAE payload. Once inside the cancer cell, the Vc linker is cleaved, releasing MMAE, which disrupts microtubule formation and induces cell death. This mechanism allows INNO-206 to target tumors while minimizing damage to healthy tissues, a major advantage in reducing the side effects commonly seen with conventional chemotherapy.

In addition to its use in cancer therapy, INNO-206 has potential applications in combination therapies. Researchers are exploring the combination of INNO-206 with immune checkpoint inhibitors or other immunotherapies to enhance the anti-tumor immune response. By selectively targeting and killing tumor cells, INNO-206 may promote the release of tumor antigens, stimulating the immune system to recognize and attack residual cancer cells. This approach is part of the growing field of immuno-oncology, where the combination of targeted therapies and immune system modulation holds the potential for more effective cancer treatments.

Another application of INNO-206 is in the development of precision medicine. The specificity of INNO-206 for tumor cells expressing the target antigen allows for a personalized treatment approach. By identifying biomarkers that predict which patients will benefit most from this targeted therapy, INNO-206 can be used to tailor treatment plans, ensuring that patients with specific tumor profiles receive the most appropriate and effective therapies. This strategy enhances the likelihood of treatment success and minimizes unnecessary exposure to toxic agents in patients who may not benefit from the drug.

1.Anti-myeloma effects of the novel anthracycline derivative INNO-206.
Sanchez E1, Li M, Wang C, Nichols CM, Li J, Chen H, Berenson JR. Clin Cancer Res. 2012 Jul 15;18(14):3856-67. doi: 10.1158/1078-0432.CCR-11-3130. Epub 2012 May 22.
PURPOSE: Doxorubicin has shown efficacy especially in combination treatment for the treatment of multiple myeloma; however, its side effects limit its use. INNO-206 is an albumin-binding prodrug of doxorubicin, which is released from albumin under acidic conditions. Because INNO-206 has not been previously evaluated in any hematologic malignancy, we determined its anti-multiple myeloma effects.
The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Historical Records: INNO-206
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