This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Aldoxorubicin
Accession Number
DB06013
Type
Small Molecule
Groups
Investigational
Description

Aldoxorubicin, an antineoplastic agents, is an albumin-binding prodrug of doxorubicin.

Structure
Thumb
Synonyms
Not Available
External IDs
INNO-206
Product Ingredients
IngredientUNIICASInChI Key
Aldoxorubicin hydrochlorideS098K6HGD91361563-03-2NGKHWQPYPXRQTM-UKFSEGPMSA-N
Categories
UNII
C28MV4IM0B
CAS number
1361644-26-9
Weight
Average: 750.758
Monoisotopic: 750.274837428
Chemical Formula
C37H42N4O13
InChI Key
OBMJQRLIQQTJLR-USGQOSEYSA-N
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
IUPAC Name
N'-[(1E)-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-1,2,3,4,6,11-hexahydrotetracen-2-yl]-2-hydroxyethylidene]-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanehydrazide
SMILES
COC1=C2C(=O)C3=C(O)C4=C(C[C@](O)(C[C@@H]4O[C@H]4C[C@H](N)[C@H](O)[C@H](C)O4)C(\CO)=N\NC(=O)CCCCCN4C(=O)C=CC4=O)C(O)=C3C(=O)C2=CC=C1

Pharmacology

Indication

Investigated for use/treatment in solid tumors.

Pharmacodynamics
Not Available
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.

TargetActionsOrganism
ADNA topoisomerase 2-alpha
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AmsacrineThe risk or severity of cardiotoxicity can be increased when Aldoxorubicin is combined with Amsacrine.
BevacizumabThe risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Aldoxorubicin.
BleomycinThe risk or severity of cardiotoxicity can be increased when Aldoxorubicin is combined with Bleomycin.
BortezomibThe risk or severity of cardiotoxicity can be increased when Aldoxorubicin is combined with Bortezomib.
BusulfanThe risk or severity of cardiotoxicity can be increased when Busulfan is combined with Aldoxorubicin.
CarmustineThe risk or severity of cardiotoxicity can be increased when Aldoxorubicin is combined with Carmustine.
CisplatinThe risk or severity of cardiotoxicity can be increased when Aldoxorubicin is combined with Cisplatin.
CladribineThe risk or severity of cardiotoxicity can be increased when Aldoxorubicin is combined with Cladribine.
CyclophosphamideThe risk or severity of cardiotoxicity can be increased when Cyclophosphamide is combined with Aldoxorubicin.
CytarabineThe risk or severity of cardiotoxicity can be increased when Aldoxorubicin is combined with Cytarabine.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D10383
ChemSpider
7986464
ChEMBL
CHEMBL2107818
Wikipedia
Aldoxorubicin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced Solid Tumors2
1CompletedTreatmentMalignant Solid Tumours1
1CompletedTreatmentMetastatic Solid Tumors1
1, 2Not Yet RecruitingTreatmentChordomas / Unresectable Malignant Neoplasm1
1, 2RecruitingTreatmentHepatocellular Carcinoma Non-resectable / Recurrent Hepatocellular Carcinoma1
1, 2RecruitingTreatmentMalignant Neoplasm of Pancreas2
1, 2RecruitingTreatmentMCRC / Metastatic Colorectal Cancers1
1, 2RecruitingTreatmentMetastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma1
1, 2RecruitingTreatmentSquamous Cell Carcinoma (SCC)1
1, 2RecruitingTreatmentTriple Negative Breast Cancer (TNBC)1
2CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / HIV positve / Hiv-positive / Kaposi s Sarcoma (KS)1
2CompletedTreatmentGlioblastomas1
2CompletedTreatmentPancreatic Ductal Adenocarcinoma1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Not Yet RecruitingTreatmentPancreatic Cancer Metastatic1
2Not Yet RecruitingTreatmentTriple Negative Breast Cancer (TNBC)1
2RecruitingTreatmentMetastatic Small Cell Lung Cancer1
2Unknown StatusTreatmentLocally Advanced Soft Tissue Sarcoma / Metastatic Soft Tissue Sarcoma / Unresectable Soft Tissue Sarcoma1
2WithdrawnTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
3CompletedTreatmentMetastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma1
Not AvailableNo Longer AvailableNot AvailableSarcomas1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.151 mg/mLALOGPS
logP1.26ALOGPS
logP0.71ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)8.2ChemAxon
pKa (Strongest Basic)9.39ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area267.84 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity189.86 m3·mol-1ChemAxon
Polarizability75.89 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
References
  1. Chawla SP, Chua VS, Hendifar AF, Quon DV, Soman N, Sankhala KK, Wieland DS, Levitt DJ: A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma. Cancer. 2015 Feb 15;121(4):570-9. doi: 10.1002/cncr.29081. Epub 2014 Oct 13. [PubMed:25312684]

Drug created on November 18, 2007 11:29 / Updated on October 01, 2018 16:55