Identification

Name
Idarubicin
Accession Number
DB01177
Description

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
Thumb
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.

Associated Conditions
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
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
  • Bacteria
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.
AcebutololThe metabolism of Idarubicin can be decreased when combined with Acebutolol.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Idarubicin.
AcetaminophenThe metabolism of Idarubicin can be decreased when combined with Acetaminophen.
AcetohexamideThe metabolism of Idarubicin can be decreased when combined with Acetohexamide.
Acetyl sulfisoxazoleThe metabolism of Idarubicin can be decreased when combined with Acetyl sulfisoxazole.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Idarubicin.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Idarubicin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

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
Idamycin - Cap 10mgCapsuleOralPfizer Canada Ulc1996-12-312006-08-02Canada
Idamycin - Cap 25mgCapsuleOralPfizer Canada Ulc1996-12-302006-08-02Canada
Idamycin - Cap 5mgCapsuleOralPfizer Canada Ulc1996-12-312006-08-02Canada
Idamycin PFSSolution1 mg/1mLIntravenousPharmacia and Upjohn Company LLC1997-02-17Not applicableUs
Idamycin PFSSolution1 mg/1mLIntravenousPharmacia and Upjohn Co.2006-02-272006-02-27Us
Idamycin PFSSolution1 mgIntravenousPfizer Canada Ulc2006-11-25Not applicableCanada
Idamycin PFSSolution1 mg/1mLIntravenousPharmacia and Upjohn Co.2006-02-272006-02-27Us
Idamycin PFSSolution1 mg/1mLIntravenousPharmacia and Upjohn Company LLC1997-02-17Not applicableUs
Idamycin PFSSolution1 mg/1mLIntravenousPharmacia and Upjohn Co.2006-02-272006-02-27Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Aj-idarubicinSolutionIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2002-10-01Not applicableUs
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousBedford Pharmaceuticals2007-05-152011-09-30Us
Idarubicin HydrochlorideInjection10 mg/10mLIntravenousAmneal Agila, Llc2013-04-302016-12-31Us
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2017-01-30Not applicableUs
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2018-01-12Not applicableUs
Idarubicin HydrochlorideInjection1 mg/1mLIntravenousSandoz Inc.2011-03-292011-03-29Us
Idarubicin HydrochlorideInjection5 mg/5mLIntravenousAmneal Agila, Llc2013-04-302016-12-31Us
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousBedford Pharmaceuticals2007-05-152011-09-30Us
Idarubicin HydrochlorideInjection, solution1 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2002-10-01Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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)

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
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
198d / 1d38 / 1d67 / 3arq / 4lb2

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentAcute Promyelocytic Leukemia (APL)1
4CompletedTreatmentAcute Myeloblastic Leukemia1
4CompletedTreatmentAcute Myeloblastic Leukemia / Myelodysplastic Syndrome1
4CompletedTreatmentAcute Promyelocytic Leukemia (APL)1
4CompletedTreatmentAdult Acute Lymphocytic Leukemia2
4Enrolling by InvitationTreatmentAcute Myeloid Leukemia (AML)1
4RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)2
4RecruitingTreatmentAPL1
4Unknown StatusPreventionAcute Promyelocytic Leukemia (APL)1
4Unknown StatusTreatmentAcute Myeloid Leukemia (AML)2

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, powder, lyophilized, for solutionIntravenous1 mg/1mL
CapsuleOral
SolutionIntravenous1 mg
SolutionIntravenous1 mg/1mL
Powder, for solutionIntravenous
SolutionIntravenous
InjectionIntravenous1 mg/1mL
InjectionIntravenous10 mg/10mL
InjectionIntravenous20 mg/20mL
InjectionIntravenous5 mg/5mL
Injection, solutionIntravenous1 mg/1mL
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
logP1.9ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)9.55ChemAxon
pKa (Strongest Basic)8.95ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area176.61 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity126.43 m3·mol-1ChemAxon
Polarizability50.33 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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000x-0393000000-ddc13e189dad3ac7e41a

Targets

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. [PubMed:17716648]
  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. [PubMed:1723369]
  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. [PubMed:8036155]
  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. [PubMed:8494991]
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. [PubMed:12034365]
  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. [PubMed:10523799]
  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. [PubMed:10203104]
  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. [PubMed:11836027]
  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. [PubMed:8036155]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

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. [PubMed:15204103]
  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. [PubMed:24492490]
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. [PubMed:15204103]

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. [PubMed:9188796]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2020 22:18

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