You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameIdarubicin
Accession NumberDB01177  (APRD00126)
TypeSmall Molecule
GroupsApproved
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. [PubChem]

Structure
Thumb
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-alpha-L-lyxo-hexopyranoside
4-Demethoxydaunomycin
4-Demethoxydaunorubicin
5,12-Naphthacenedione, 9-acetyl-7-((3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-, (7S-cis)-
Idarubicina
Idarubicine
Idarubicinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aj-idarubicinsolution1 mgintravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Idamycin - Cap 10mgcapsule10 mgoralPfizer Canada Inc1996-12-312006-08-02Canada
Idamycin - Cap 25mgcapsule25 mgoralPfizer Canada Inc1996-12-302006-08-02Canada
Idamycin - Cap 5mgcapsule5 mgoralPfizer Canada Inc1996-12-312006-08-02Canada
Idamycin PFSsolution1 mg/mLintravenousPharmacia and Upjohn Company1997-02-17Not applicableUs
Idamycin PFSsolution1 mgintravenousPfizer Canada Inc2006-11-25Not applicableCanada
Idamycin PFSsolution1 mg/mLintravenousPharmacia and Upjohn Company1997-02-17Not applicableUs
Idamycin PFSsolution1 mg/mLintravenousPharmacia and Upjohn Company1997-02-17Not applicableUs
Idamycin Powder -5mg/vialpowder for solution5 mgintravenousPfizer Canada Inc1995-12-312014-03-21Canada
Idamycin Powder -10mg/vialpowder for solution10 mgintravenousPfizer Canada Inc1995-12-312014-03-21Canada
Idamycin Pws 10mg/vialpowder for solution10 mgintravenousAdria Laboratories Of Canada Ltd.1991-12-311996-09-10Canada
Idamycin Pws 5mg/vialpowder for solution5 mgintravenousAdria Laboratories Of Canada Ltd.1991-12-311996-09-10Canada
Idarubicinsolution1 mgintravenousPfizer Canada Inc2014-11-04Not applicableCanada
Idarubicin Hydrochloride Injectionsolution1 mgintravenousFresenius Kabi Canada Ltd2010-04-13Not applicableCanada
Idarubicin Hydrochloride Injectionsolution1 mgintravenousMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Idarubicin Hydrochlorideinjection, solution1 mg/mLintravenousTeva Parenteral Medicines, Inc.2002-10-01Not applicableUs
Idarubicin Hydrochlorideinjection1 mg/mLintravenousSandoz Inc2011-03-29Not applicableUs
Idarubicin Hydrochlorideinjection, solution1 mg/mLintravenousFresenius Kabi USA, LLC2009-08-11Not applicableUs
Idarubicin Hydrochlorideinjection20 mg/20mLintravenousAmneal Agila, Llc2013-04-30Not applicableUs
Idarubicin Hydrochlorideinjection10 mg/10mLintravenousAmneal Agila, Llc2013-04-30Not applicableUs
Idarubicin Hydrochlorideinjection5 mg/5mLintravenousAmneal Agila, Llc2013-04-30Not applicableUs
Idarubicin Hydrochlorideinjection, solution1 mg/mLintravenousTeva Parenteral Medicines, Inc.2002-10-01Not applicableUs
Idarubicin Hydrochlorideinjection, solution1 mg/mLintravenousTeva Parenteral Medicines, Inc.2002-10-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
IdamycinNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Idarubicin Hydrochloride
Thumb
  • InChI Key: JVHPTYWUBOQMBP-RVFAQHLVSA-N
  • Monoisotopic Mass: 533.145259206
  • Average Mass: 533.955
DBSALT000341
Categories
UNIIZRP63D75JW
CAS number58957-92-9
WeightAverage: 497.4939
Monoisotopic: 497.168581467
Chemical FormulaC26H27NO9
InChI KeyInChIKey=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[[email protected]](C[[email protected]](N)[C@@H]1O)O[[email protected]]1C[C@@](O)(CC2=C1C(O)=C1C(=O)C3=CC=CC=C3C(=O)C1=C2O)C(C)=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassAnthracyclines
Sub ClassNot Available
Direct ParentAnthracyclines
Alternative Parents
Substituents
  • Anthracyclinone-skeleton
  • Anthracycline
  • Tetracenequinone
  • 1,4-anthraquinone
  • 9,10-anthraquinone
  • Anthracene
  • Amino sugar
  • Tetralin
  • Aryl ketone
  • Hydroquinone
  • Amino saccharide
  • Benzenoid
  • Oxane
  • Monosaccharide
  • Saccharide
  • Vinylogous acid
  • Tertiary alcohol
  • Alpha-hydroxy ketone
  • Secondary alcohol
  • Polyol
  • Ketone
  • 1,2-aminoalcohol
  • Oxacycle
  • Organoheterocyclic compound
  • Acetal
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of acute myeloid leukemia (AML) in adults. This includes French-American-British (FAB) classifications M1 through M7.
PharmacodynamicsIdarubicin 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 actionIdarubicin 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding97%
MetabolismNot Available
Route of eliminationThe drug is eliminated predominately by biliary and to a lesser extent by renal excretion, mostly in the form of idarubicinol.
Half life22 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
  • Bacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral10 mg
Capsuleoral25 mg
Capsuleoral5 mg
Solutionintravenous1 mg/mL
Solutionintravenous1 mg
Powder for solutionintravenous10 mg
Powder for solutionintravenous5 mg
Injectionintravenous1 mg/mL
Injectionintravenous10 mg/10mL
Injectionintravenous20 mg/20mL
Injectionintravenous5 mg/5mL
Injection, solutionintravenous1 mg/mL
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.
PatentsNot Available
Properties
StateSolid
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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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 ReferencesNot Available
External Links
ATC CodesL01DB06
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
BevacizumabBevacizumab may increase the cardiotoxic activities of Idarubicin.
ClozapineThe risk or severity of adverse effects can be increased when Idarubicin is combined with Clozapine.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Idarubicin.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Idarubicin.
DigoxinDigoxin may decrease the cardiotoxic activities of Idarubicin.
LeflunomideThe risk or severity of adverse effects can be increased when Idarubicin is combined with Leflunomide.
LumacaftorThe serum concentration of Idarubicin can be decreased when it is combined with Lumacaftor.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Idarubicin.
NatalizumabThe risk or severity of adverse effects can be increased when Idarubicin is combined with Natalizumab.
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Idarubicin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Idarubicin.
RanolazineThe serum concentration of Idarubicin can be increased when it is combined with Ranolazine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Idarubicin.
SaquinavirThe serum concentration of Idarubicin can be increased when it is combined with Saquinavir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Idarubicin.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Idarubicin.
TesmilifeneThe serum concentration of Idarubicin can be decreased when it is combined with Tesmilifene.
TofacitinibIdarubicin may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Idarubicin.
VerapamilThe serum concentration of Idarubicin can be increased when it is combined with Verapamil.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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
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 segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
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
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
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, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
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 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13