Idarubicin

Identification

Summary

Idarubicin is an anthracycline antineoplastic agent used to treat acute myeloid leukemia (AML) in adults.

Brand Names
Idamycin
Generic Name
Idarubicin
DrugBank Accession Number
DB01177
Background

An orally administered anthracycline antineoplastic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with the potential for reduced cardiac toxicity.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 497.4939
Monoisotopic: 497.168581467
Chemical Formula
C26H27NO9
Synonyms
  • (1S,3S)-3-acetyl-3,5,12-trihydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydronaphthacen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside
  • 4-Demethoxydaunomycin
  • 4-Demethoxydaunorubicin
  • Idarubicin
  • Idarubicina
  • Idarubicine
  • Idarubicinum

Pharmacology

Indication

For the treatment of acute myeloid leukemia (AML) in adults. This includes French-American-British (FAB) classifications M1 through M7.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatAcute myeloid leukemia••• ••••••••••••••
Used in combination to treatAcute myeloid leukemia•••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Idarubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Idarubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Idarubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.

Mechanism of action

Idarubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Idarubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

TargetActionsOrganism
ADNA
intercalation
Humans
ADNA topoisomerase 2-alpha
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

97%

Metabolism
Not Available
Route of elimination

The drug is eliminated predominately by biliary and to a lesser extent by renal excretion, mostly in the form of idarubicinol.

Half-life

22 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe metabolism of Idarubicin can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Idarubicin.
AbirateroneThe metabolism of Idarubicin can be decreased when combined with Abiraterone.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Idarubicin.
AcebutololThe metabolism of Idarubicin can be decreased when combined with Acebutolol.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Idarubicin hydrochloride5VV3MDU5IE57852-57-0JVHPTYWUBOQMBP-RVFAQHLVSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IdamycinInjection, powder, lyophilized, for solution1 mg/1mLIntravenousPharmacia and Upjohn Company LLC1990-09-272010-06-01US flag
Idamycin - Cap 10mgCapsule10 mgOralPfizer Canada Ulc1996-12-312006-08-02Canada flag
Idamycin - Cap 25mgCapsule25 mgOralPfizer Canada Ulc1996-12-302006-08-02Canada flag
Idamycin - Cap 5mgCapsule5 mgOralPfizer Canada Ulc1996-12-312006-08-02Canada flag
Idamycin PFSSolution1 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc1997-02-17Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Aj-idarubicinSolution1 mg / mLIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousFresenius Kabi USA, LLC2009-08-112019-08-31US flag
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2018-01-12Not applicableUS flag
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousBedford Pharmaceuticals2007-05-152011-09-30US flag
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2017-01-30Not applicableUS flag

Categories

ATC Codes
L01DB06 — Idarubicin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as anthracyclines. These are polyketides containing a tetracenequinone ring structure with a sugar attached by glycosidic linkage.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Anthracyclines
Sub Class
Not Available
Direct Parent
Anthracyclines
Alternative Parents
Tetracenequinones / Aminoglycosides / Anthraquinones / Hexoses / O-glycosyl compounds / Tetralins / Aryl ketones / Oxanes / Vinylogous acids / Tertiary alcohols
show 10 more
Substituents
1,2-aminoalcohol / 1,4-anthraquinone / 9,10-anthraquinone / Acetal / Alcohol / Alpha-hydroxy ketone / Amine / Amino saccharide / Aminoglycoside core / Anthracene
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monosaccharide derivative, anthracycline antibiotic, deoxy hexoside (CHEBI:42068)
Affected organisms
  • Humans and other mammals
  • Bacteria

Chemical Identifiers

UNII
ZRP63D75JW
CAS number
58957-92-9
InChI Key
XDXDZDZNSLXDNA-TZNDIEGXSA-N
InChI
InChI=1S/C26H27NO9/c1-10-21(29)15(27)7-17(35-10)36-16-9-26(34,11(2)28)8-14-18(16)25(33)20-19(24(14)32)22(30)12-5-3-4-6-13(12)23(20)31/h3-6,10,15-17,21,29,32-34H,7-9,27H2,1-2H3/t10-,15-,16-,17-,21+,26-/m0/s1
IUPAC Name
(7S,9S)-9-acetyl-7-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,9,11-trihydroxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione
SMILES
C[C@@H]1O[C@H](C[C@H](N)[C@@H]1O)O[C@H]1C[C@@](O)(CC2=C1C(O)=C1C(=O)C3=CC=CC=C3C(=O)C1=C2O)C(C)=O

References

Synthesis Reference

Marco Villa, Roberto Arosio, Roberta Fretta, Nicola Diulgheroff, "Synthesis of idarubicin aglycone." U.S. Patent US20060047108, issued March 02, 2006.

US20060047108
General References
Not Available
Human Metabolome Database
HMDB0015308
PubChem Compound
42890
PubChem Substance
46506973
ChemSpider
39117
BindingDB
58490
RxNav
5650
ChEBI
42068
ChEMBL
CHEMBL1117
ZINC
ZINC000003920266
Therapeutic Targets Database
DAP000050
PharmGKB
PA449961
PDBe Ligand
DM5
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Idarubicin
PDB Entries
198d / 1d38 / 1d67 / 3arq / 4lb2

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAcute Myeloid Leukemia1
4CompletedTreatmentAcute Myeloid Leukemia / Myelodysplastic Syndrome1
4CompletedTreatmentAcute Promyelocytic Leukemia1
4CompletedTreatmentLeukemia, Lymphocytic, Acute, Adult4
4RecruitingTreatmentAcute Lymphoblastic Leukemia (ALL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Greenstone LLC
  • Pfizer Inc.
  • Pharmacia Inc.
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
Injection, solution1 mg/1ml
Injection, powder, lyophilized, for solutionIntravenous1 mg/1mL
SolutionIntravenous1 mg/1mL
Powder, for solutionIntravenous10 mg / vial
Powder, for solutionIntravenous5 mg / vial
Injection, powder, lyophilized, for solutionParenteral10 mg
Injection, powder, lyophilized, for solutionIntravenous20 mg
SolutionIntravenous1 mg / mL
Injection, solutionParenteral10 mg/10ml
Injection, solutionParenteral20 mg/20ml
Injection, solutionParenteral5 mg/5ml
Injection, solution, concentrateIntravenous1 mg/ml
InjectionIntravenous1 mg/1mL
InjectionIntravenous10 mg/10mL
InjectionIntravenous20 mg/20mL
InjectionIntravenous5 mg/5mL
Injection, solutionIntravenous1 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg
Injection, powder, lyophilized, for solutionIntravenous5 mg
Injection, solutionIntravenous10 MG/10ml
Injection, solutionIntravenous20 MG/20ml
Injection, solutionIntravenous5 MG/5ml
Solution, concentrateIntravenous10 mg
Injection, solution
Injection, solution, concentrateIntravenous; Parenteral1 MG/ML
SolutionIntravenous5.000 mg
SolutionParenteral5.000 mg
Injection, powder, for solutionIntravenous; Parenteral10 MG
Injection, powder, for solutionIntravenous; Parenteral5 MG/5ML
Injection, powder, for solutionParenteral10 mg
CapsuleOral10 mg
CapsuleOral25 mg
CapsuleOral5 mg
Injection, solutionIntravenous
Injection, powder, for solutionIntravenous10 mg
Injection, powder, for solutionIntravenous5 mg
SolutionIntravenous1 mg
Prices
Unit descriptionCostUnit
Idamycin pfs 1 mg/ml vial60.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.772 mg/mLALOGPS
logP1.69ALOGPS
logP1.52Chemaxon
logS-2.8ALOGPS
pKa (Strongest Acidic)8.04Chemaxon
pKa (Strongest Basic)10.04Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count10Chemaxon
Hydrogen Donor Count5Chemaxon
Polar Surface Area176.61 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity126.43 m3·mol-1Chemaxon
Polarizability50.84 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.5153
Blood Brain Barrier-0.975
Caco-2 permeable-0.7492
P-glycoprotein substrateSubstrate0.7862
P-glycoprotein inhibitor INon-inhibitor0.7328
P-glycoprotein inhibitor IINon-inhibitor0.956
Renal organic cation transporterNon-inhibitor0.9214
CYP450 2C9 substrateNon-substrate0.8004
CYP450 2D6 substrateNon-substrate0.8937
CYP450 3A4 substrateSubstrate0.5419
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9439
CYP450 2D6 inhibitorNon-inhibitor0.9382
CYP450 2C19 inhibitorNon-inhibitor0.9316
CYP450 3A4 inhibitorNon-inhibitor0.9514
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9516
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9456
BiodegradationNot ready biodegradable0.9762
Rat acute toxicity4.3474 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9896
hERG inhibition (predictor II)Non-inhibitor0.882
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0006-9001300000-2de3fa2c7773861d551e
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000x-0393000000-ddc13e189dad3ac7e41a
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0309700000-7a7d8a924aed8ebfbe88
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00dj-0009000000-ba26d10baeadbf8aa0ae
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0gx0-0409700000-7b377bf5841ca8e638d3
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0009000000-651028504c2ea7acc4f3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-052k-0309400000-2d1611c3fc1db092a92c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00ke-0403900000-0dd6c9dfe81b45e61706
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-220.902591
predicted
DarkChem Lite v0.1.0
[M-H]-216.498891
predicted
DarkChem Lite v0.1.0
[M-H]-208.91301
predicted
DeepCCS 1.0 (2019)
[M+H]+221.521091
predicted
DarkChem Lite v0.1.0
[M+H]+218.086891
predicted
DarkChem Lite v0.1.0
[M+H]+210.73793
predicted
DeepCCS 1.0 (2019)
[M+Na]+221.931591
predicted
DarkChem Lite v0.1.0
[M+Na]+220.054891
predicted
DarkChem Lite v0.1.0
[M+Na]+216.34373
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Intercalation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Zahraei Z, Rabbani-Chadegani A: A comparison of the effect of anticancer drugs, idarubicin and adriamycin, on soluble chromatin. Eur J Pharmacol. 2007 Dec 1;575(1-3):28-33. Epub 2007 Jul 31. [Article]
  2. Hollingshead LM, Faulds D: Idarubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs. 1991 Oct;42(4):690-719. [Article]
  3. Bigioni M, Zunino F, Capranico G: Base mutation analysis of topoisomerase II-idarubicin-DNA ternary complex formation. Evidence for enzyme subunit cooperativity in DNA cleavage. Nucleic Acids Res. 1994 Jun 25;22(12):2274-81. [Article]
  4. Fukushima T, Ueda T, Uchida M, Nakamura T: Action mechanism of idarubicin (4-demethoxydaunorubicin) as compared with daunorubicin in leukemic cells. Int J Hematol. 1993 Apr;57(2):121-30. [Article]
Kind
Protein
Organism
Humans
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. Willmore E, Errington F, Tilby MJ, Austin CA: Formation and longevity of idarubicin-induced DNA topoisomerase II cleavable complexes in K562 human leukaemia cells. Biochem Pharmacol. 2002 May 15;63(10):1807-15. [Article]
  2. Zhou R, Wang Y, Gruber A, Larsson R, Castanos-Velez E, Liliemark E: Topoisomerase II-mediated alterations of K562 drug resistant sublines. Med Oncol. 1999 Sep;16(3):191-8. [Article]
  3. De Renzo A, Santoro LF, Notaro R, Pane F, Buonaiuto MR, Luciano L, Rotoli B: Acute promyelocytic leukemia after treatment for non-Hodgkin's lymphoma with drugs targeting topoisomerase II. Am J Hematol. 1999 Apr;60(4):300-4. [Article]
  4. Gonzalez-Cid M, Fundia AF, Cuello MT, Larripa I: Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes. Toxicology. 2002 Feb 28;171(2-3):215-22. [Article]
  5. Bigioni M, Zunino F, Capranico G: Base mutation analysis of topoisomerase II-idarubicin-DNA ternary complex formation. Evidence for enzyme subunit cooperativity in DNA cleavage. Nucleic Acids Res. 1994 Jun 25;22(12):2274-81. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Colburn DE, Giles FJ, Oladovich D, Smith JA: In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21. doi: 10.1080/10245330410001701585. [Article]
  2. Cizkova K, Konieczna A, Erdosova B, Ehrmann J: Time-dependent expression of cytochrome p450 epoxygenases during human prenatal development. Organogenesis. 2014 Jan 1;10(1):53-61. doi: 10.4161/org.27911. Epub 2014 Feb 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Colburn DE, Giles FJ, Oladovich D, Smith JA: In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21. doi: 10.1080/10245330410001701585. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Heijn M, Hooijberg JH, Scheffer GL, Szabo G, Westerhoff HV, Lankelma J: Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. Biochim Biophys Acta. 1997 May 22;1326(1):12-22. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48