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Record Information
Version2.0
Creation Date2009-07-21 20:27:25 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2861
Identification
Common NameDaunorubicin
ClassSmall Molecule
DescriptionDaunorubicin is only found in individuals that have used or taken this drug. It is a very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of leukemia and other neoplasms. [PubChem]Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin 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.
Compound Type
  • Amine
  • Antibiotic
  • Antibiotic, Antineoplastic
  • Antineoplastic Agent
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-Daunomycin
(8S-cis)-8-Acetyl-10-((3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyrannosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-napthacenedione
Acetyladriamycin
Cerubidin
Cerubidine
Daunoblastin
Daunoblastina
Daunomycin
Daunorrubicina
Daunorubicina
Daunorubicine
Daunorubicinum
DaunoXome
Leukaemomycin C
Maxidauno
Rubidomycin
Chemical FormulaC27H29NO10
Average Molecular Mass527.520 g/mol
Monoisotopic Mass527.179 g/mol
CAS Registry Number20830-81-3
IUPAC Name(8S,10S)-8-acetyl-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione
Traditional Namedaunorubicin
SMILES[H][C@]1(N)C[C@]([H])(O[C@@]2([H])C[C@@](O)(CC3=C(O)C4=C(C(O)=C23)C(=O)C2=C(C=CC=C2OC)C4=O)C(C)=O)O[C@@]([H])(C)[C@@]1([H])O
InChI IdentifierInChI=1S/C27H29NO10/c1-10-22(30)14(28)7-17(37-10)38-16-9-27(35,11(2)29)8-13-19(16)26(34)21-20(24(13)32)23(31)12-5-4-6-15(36-3)18(12)25(21)33/h4-6,10,14,16-17,22,30,32,34-35H,7-9,28H2,1-3H3/t10-,14-,16-,17-,22+,27-/m0/s1
InChI KeyInChIKey=STQGQHZAVUOBTE-VGBVRHCVSA-N
Chemical Taxonomy
Description 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
  • Anthracycline
  • Anthracyclinone-skeleton
  • Aminoglycoside core
  • Tetracenequinone
  • 9,10-anthraquinone
  • 1,4-anthraquinone
  • Anthracene
  • Hexose monosaccharide
  • Glycosyl compound
  • O-glycosyl compound
  • Tetralin
  • Aryl ketone
  • Anisole
  • Amino saccharide
  • Alkyl aryl ether
  • Benzenoid
  • Oxane
  • Monosaccharide
  • Vinylogous acid
  • Tertiary alcohol
  • Alpha-hydroxy ketone
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Ketone
  • Organoheterocyclic compound
  • Acetal
  • Ether
  • Polyol
  • Oxacycle
  • Primary amine
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Primary aliphatic amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point208-209°C
Boiling PointNot Available
Solubility39.2 mg/L
LogP1.83
Predicted Properties
PropertyValueSource
Water Solubility0.63 g/LALOGPS
logP1.68ALOGPS
logP1.73ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)9.53ChemAxon
pKa (Strongest Basic)8.94ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area185.84 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity132.89 m³·mol⁻¹ChemAxon
Polarizability52.94 ųChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9200300000-b86566e84001e30da377JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0a4i-9200135000-1c14f3df000eec108899JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-00di-0229100000-35f2df54929348a28ee4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-03k9-0419110000-70d2a081fbad20bd67d7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-00di-0219100000-b592d3a84cac9ef0b6cdJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-01sj-0009280000-938bd3eaade51c04aafdJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0319000000-543d7f990f443c45a59aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-5119000000-a692f22291ba5dcb0808JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-1104190000-47330bcd3826d8820bc0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-002b-2109420000-a7be1508cced736226fcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-3109100000-13452a25c0c03df2d319JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03e9-0409240000-c2e5b799e5c588ee6f3eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-2709330000-ed3234db0e99dfed2fefJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03e9-4922200000-c1091039c837788e6ffcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0009000000-294a27e0915e38aa66faJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0fuj-0009000000-92a5bfac85109e9f056cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0301-0009010000-08c42b7b4f498ddf12ceJSpectraViewer
Toxicity Profile
Route of ExposureIntravenous
Mechanism of ToxicityDaunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin 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.
MetabolismHepatic Route of Elimination: Twenty-five percent of an administered dose of daunorubicin hydrochloride is eliminated in an active form by urinary excretion and an estimated 40% by biliary excretion. Half Life: 18.5 hours
Toxicity ValuesLD50=20 mg/kg (mice, IV); LD50=13 mg/kg (rat, IV)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (6)
Uses/SourcesFor remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.
Minimum Risk LevelNot Available
Health EffectsAntibiotic resistance. Toxic manifestations of Daunorubicin include bone marrow depression, stomatitis, alopecia, gastrointestinal disturbances, and dermatological manifestations. Cardiac toxicity is a pecular effect. (1)
Symptomssymptoms include gastrointestinal disturbances. (1)
TreatmentInfuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00694
HMDB IDHMDB14832
PubChem Compound ID30323
ChEMBL IDCHEMBL178
ChemSpider ID28163
KEGG IDC01907
UniProt IDNot Available
OMIM ID
ChEBI ID4330
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDaunorubicin
PDB IDDM1
ACToR IDNot Available
Wikipedia LinkDaunorubicin
References
Synthesis Reference

Sylvie Pinnert, Leon Ninet, Jean Preud’Homme, “Antibiotic daunorubicin and its preparation.” U.S. Patent US3989598, issued March, 1965.

MSDSLink
General References
  1. Mayatepek E, Hoffmann GF, Baumgartner R, Schulze A, Jakobs C, Trefz FK, Bremer HJ: Atypical vitamin B12-unresponsive methylmalonic aciduria in sibship with severe progressive encephalomyelopathy: a new genetic disease? Eur J Pediatr. 1996 May;155(5):398-403. [8741039 ]
  2. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [15509185 ]
  3. Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2010; CCIS Volume 143, edition expires Feb, 2010. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2010; CCIS Volume 143, edition expires Feb, 2010.
  4. Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1243
  5. Drugs.com [Link]
  6. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.95 uMNot AvailableBindingDB 50368352
IC508 uMNot AvailableBindingDB 50368352
References
  1. Renes J, de Vries EG, Nienhuis EF, Jansen PL, Muller M: ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1. Br J Pharmacol. 1999 Feb;126(3):681-8. [10188979 ]
  2. Hooijberg JH, Pinedo HM, Vrasdonk C, Priebe W, Lankelma J, Broxterman HJ: The effect of glutathione on the ATPase activity of MRP1 in its natural membranes. FEBS Lett. 2000 Mar 3;469(1):47-51. [10708754 ]
  3. Marbeuf-Gueye C, Salerno M, Quidu P, Garnier-Suillerot A: Inhibition of the P-glycoprotein- and multidrug resistance protein-mediated efflux of anthracyclines and calceinacetoxymethyl ester by PAK-104P. Eur J Pharmacol. 2000 Mar 17;391(3):207-16. [10729360 ]
  4. Evers R, Kool M, Smith AJ, van Deemter L, de Haas M, Borst P: Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1 Pgp-, MRP1- and MRP2-mediated transport. Br J Cancer. 2000 Aug;83(3):366-74. [10917553 ]
  5. Evers R, de Haas M, Sparidans R, Beijnen J, Wielinga PR, Lankelma J, Borst P: Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83. [10917554 ]
  6. Loe DW, Almquist KC, Cole SP, Deeley RG: ATP-dependent 17 beta-estradiol 17-(beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. J Biol Chem. 1996 Apr 19;271(16):9683-9. [8621644 ]
  7. 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. [9188796 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory111 uMNot AvailableBindingDB 50368352
References
  1. Perez-Victoria JM, Chiquero MJ, Conseil G, Dayan G, Di Pietro A, Barron D, Castanys S, Gamarro F: Correlation between the affinity of flavonoids binding to the cytosolic site of Leishmania tropica multidrug transporter and their efficiency to revert parasite resistance to daunomycin. Biochemistry. 1999 Feb 9;38(6):1736-43. [10026252 ]
  2. Pallis M, Turzanski J, Harrison G, Wheatley K, Langabeer S, Burnett AK, Russell NH: Use of standardized flow cytometric determinants of multidrug resistance to analyse response to remission induction chemotherapy in patients with acute myeloblastic leukaemia. Br J Haematol. 1999 Feb;104(2):307-12. [10050713 ]
  3. Chiodini B, Bassan R, Barbui T: Cellular uptake and antiproliferative effects of therapeutic concentrations of idarubicin or daunorubicin and their alcohol metabolites, with or without cyclosporin A, in MDR1+ human leukemic cells. Leuk Lymphoma. 1999 May;33(5-6):485-97. [10342576 ]
  4. Romsicki Y, Sharom FJ: The membrane lipid environment modulates drug interactions with the P-glycoprotein multidrug transporter. Biochemistry. 1999 May 25;38(21):6887-96. [10346910 ]
  5. Hiessbock R, Wolf C, Richter E, Hitzler M, Chiba P, Kratzel M, Ecker G: Synthesis and in vitro multidrug resistance modulating activity of a series of dihydrobenzopyrans and tetrahydroquinolines. J Med Chem. 1999 Jun 3;42(11):1921-6. [10354400 ]
  6. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. [12134945 ]
3. DNA
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. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [6380596 ]
  2. Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [1963303 ]
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. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [6380596 ]
  2. Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [1963303 ]
General Function:
Protein kinase c binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Gene Name:
TOP2B
Uniprot ID:
Q02880
Molecular Weight:
183265.825 Da
References
  1. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [6380596 ]
  2. Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [1963303 ]
General Function:
Zinc ion binding
Specific Function:
Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
Gene Name:
MMP2
Uniprot ID:
P08253
Molecular Weight:
73881.695 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.9 uMNot AvailableBindingDB 50368352
References
  1. Bols M, Binderup L, Hansen J, Rasmussen P: Inhibition of collagenase by aranciamycin and aranciamycin derivatives. J Med Chem. 1992 Jul 24;35(15):2768-71. [1322986 ]
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory49.4 uMNot AvailableBindingDB 50368352
References
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. [12134946 ]