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Identification
Name Daunorubicin
Accession Number DB00694 (APRD00521)
Type small molecule
Groups approved
Description

A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of leukemia and other neoplasms. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Acetyladriamycin
Anthracyline
Antibiotics From Streptomyces Coeruleorubidus
Cerubidin
Cerubidine
Daunamycin
Daunarubicinum
Daunoblastin
Daunomycin
Daunomycin Hydrochloride
Daunomycin, Hydrochloride
Daunorrubicina
Daunorubicin Hcl
Daunorubicin Hydrochloride
Daunorubicin, Hydrochloride
Daunorubicine
Daunorubicinum [INN-Latin]
Daunoxome
DM1
Leukaemomycin C
Ondena
Rcra Waste No. U059
Rp 13057 Hydrochloride
Rubidomycin
Rubidomycin Hydrochloride
Rubomycin C
First Prev Next Last
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antibiotics
  • Antibiotics, Antineoplastic
CAS number 20830-81-3
Weight Average: 527.5199
Monoisotopic: 527.179146153
Chemical Formula C27H29NO10
InChI Key InChIKey=STQGQHZAVUOBTE-VGBVRHCVSA-N
InChI
InChI=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
Plain Text
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
SMILES
COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(C)=O)C(O)=C1C2=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Anthracyclines
Substructures
  • Anthracyclines
  • Hydroxy Compounds
  • Pyrans
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Acetals and Derivatives
  • Phenols and Derivatives
  • Benzoquinones
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Naphthoquinones
  • Anthraquinones
  • Anthracenes
  • Hydroquinones
  • Amino Alcohols
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Benzoyl Derivatives
  • Cyclohexenes and Derivatives
  • Phenyl Esters
  • Ketones
Pharmacology
Indication For remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.
Pharmacodynamics Daunorubicin 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. Daunorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Daunorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.
Mechanism of action 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding 97% binding-albumin
Metabolism Hepatic
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
Clearance Not Available
Toxicity LD50=20 mg/kg (mice, IV); LD50=13 mg/kg (rat, IV)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Gilead sciences inc
  • Bedford laboratories div ben venue laboratories inc
  • Sanofi aventis us llc
  • Wyeth ayerst research
  • App pharmaceuticals llc
  • Teva parenteral medicines inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Prices
Unit description Cost Unit
Daunorubicin 20 mg/4 ml vial 163.01 USD ml
Cerubidine 20 mg vial 50.4 USD vial
Daunorubicin 50 mg/10 ml vial 42.45 USD ml
Daunoxome 2 mg/ml vial 13.06 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 208-209 °C PhysProp
water solubility 39.2 mg/L Not Available
logP 1.83 SANGSTER (1993)
Predicted Properties
Property Value Source
water solubility 6.27e-01 g/l ALOGPS
logP 1.68 ALOGPS
logP 1.73 ChemAxon
logS -2.9 ALOGPS
pKa (strongest acidic) 9.53 ChemAxon
pKa (strongest basic) 8.94 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 11 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 185.84 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 132.89 ChemAxon
polarizability 52.94 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C01907 Link_out
PubChem Compound 30323 Link_out
PubChem Substance 46508433 Link_out
ChemSpider 28163 Link_out
ChEBI 4330 Link_out
ChEMBL 4330 Link_out
Therapeutic Targets Database DNC000517 Link_out
PharmGKB PA449212 Link_out
HET BNR Link_out
Drug Product Database 2231420 Link_out
RxList http://www.rxlist.com/cgi/generic2/daunorubicin.htm Link_out
Drugs.com http://www.drugs.com/cdi/daunorubicin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Daunorubicin Link_out
ATC Codes
  • L01DB02
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label Not Available
MSDS show (36.2 KB)
Interactions
Drug Interactions
Drug Interaction
Trastuzumab Trastuzumab may increase the cardiotoxicity of Daunorubicin. Signs and symptoms of cardiac dysfunction should be monitored for frequently. Increased risk of heart failure. Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available
Targets

1. DNA

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.

Gene Sequence: FASTA

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. Pubmed
  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. Pubmed

2. DNA topoisomerase 2-alpha

Pharmacological action: yes
Actions: inhibitor

Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks

Organism class: human
UniProt ID: P11388 Link_out
Gene: TOP2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed

3. DNA topoisomerase 2-beta

Pharmacological action: yes
Actions: inhibitor

Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks

Organism class: human
UniProt ID: Q02880 Link_out
Gene: TOP2B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Actions: inducer

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang T, Chen FY, Han JY, Shao NX, Ou-Yuang RR: [Study of CYP3A5 in drug resistance mechanisms in acute leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2003 Jun;24(6):286-9. Pubmed

3. Cytochrome P450 1A2

Actions: substrate

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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 1A1

Actions: substrate

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

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 1B1

Actions: inhibitor

Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development

UniProt ID: Q16678 Link_out
Gene: CYP1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

6. Xanthine dehydrogenase/oxidase

Actions: substrate

This enzyme can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups

UniProt ID: P47989 Link_out
Gene: XDH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yee SB, Pritsos CA: Comparison of oxygen radical generation from the reductive activation of doxorubicin, streptonigrin, and menadione by xanthine oxidase and xanthine dehydrogenase. Arch Biochem Biophys. 1997 Nov 15;347(2):235-41. Pubmed
  2. Yee SB, Pritsos CA: Reductive activation of doxorubicin by xanthine dehydrogenase from EMT6 mouse mammary carcinoma tumors. Chem Biol Interact. 1997 May 2;104(2-3):87-101. Pubmed

7. NADPH--cytochrome P450 reductase

Actions: substrate

This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5

UniProt ID: P16435 Link_out
Gene: POR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bachur NR, Gordon SL, Gee MV, Kon H: NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals. Proc Natl Acad Sci U S A. 1979 Feb;76(2):954-7. Pubmed
  2. Di Re J, Lee C, Riddick DS: Lack of mechanism-based inactivation of rat hepatic microsomal cytochromes P450 by doxorubicin. Can J Physiol Pharmacol. 1999 Aug;77(8):589-97. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou G, Kuo MT: Wild-type p53-mediated induction of rat mdr1b expression by the anticancer drug daunorubicin. J Biol Chem. 1998 Jun 19;273(25):15387-94. Pubmed
  2. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. Pubmed
  3. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
  4. 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. Pubmed
  5. Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. Pubmed
  6. Tang F, Ouyang H, Yang JZ, Borchardt RT: Bidirectional transport of rhodamine 123 and Hoechst 33342, fluorescence probes of the binding sites on P-glycoprotein, across MDCK-MDR1 cell monolayers. J Pharm Sci. 2004 May;93(5):1185-94. Pubmed
  7. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. Pubmed
  8. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. Pubmed
  9. Takara K, Sakaeda T, Kakumoto M, Tanigawara Y, Kobayashi H, Okumura K, Ohnishi N, Yokoyama T: Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport. Oncol Res. 2009;17(11-12):527-33. Pubmed
  10. Borska S, Sopel M, Chmielewska M, Zabel M, Dziegiel P: Quercetin as a potential modulator of P-glycoprotein expression and function in cells of human pancreatic carcinoma line resistant to daunorubicin. Molecules. 2010 Feb 9;15(2):857-70. Pubmed
  11. 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. Pubmed
  12. 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. Pubmed
  13. 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. Pubmed
  14. 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. Pubmed
  15. 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. Pubmed

2. Multidrug resistance-associated protein 1

Actions: substrate, inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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
  3. Priebe W, Krawczyk M, Kuo MT, Yamane Y, Savaraj N, Ishikawa T: Doxorubicin- and daunorubicin-glutathione conjugates, but not unconjugated drugs, competitively inhibit leukotriene C4 transport mediated by MRP/GS-X pump. Biochem Biophys Res Commun. 1998 Jun 29;247(3):859-63. Pubmed
  4. Godinot N, Iversen PW, Tabas L, Xia X, Williams DC, Dantzig AH, Perry WL 3rd: Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey. Mol Cancer Ther. 2003 Mar;2(3):307-16. Pubmed
  5. Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG: Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos. 2003 Aug;31(8):1016-26. Pubmed
  6. Versantvoort CH, Broxterman HJ, Lankelma J, Feller N, Pinedo HM: Competitive inhibition by genistein and ATP dependence of daunorubicin transport in intact MRP overexpressing human small cell lung cancer cells. Biochem Pharmacol. 1994 Sep 15;48(6):1129-36. Pubmed
  7. Yazaki K, Yamanaka N, Masuno T, Konagai S, Shitan N, Kaneko S, Ueda K, Sato F: Heterologous expression of a mammalian ABC transporter in plant and its application to phytoremediation. Plant Mol Biol. 2006 Jun;61(3):491-503. Pubmed
  8. Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SP, Deeley RG: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53. Pubmed
  9. Nabekura T, Yamaki T, Hiroi T, Ueno K, Kitagawa S: Inhibition of anticancer drug efflux transporter P-glycoprotein by rosemary phytochemicals. Pharmacol Res. 2010 Mar;61(3):259-63. Epub 2009 Nov 26. Pubmed
  10. 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. Pubmed
  11. 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. Pubmed
  12. 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. Pubmed
  13. 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. Pubmed
  14. 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. Pubmed

3. Canalicular multispecific organic anion transporter 1

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed

4. Solute carrier family 22 member 2

Actions: substrate

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out
Gene: SLC22A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Pan BF, Sweet DH, Pritchard JB, Chen R, Nelson JA: A transfected cell model for the renal toxin transporter, rOCT2. Toxicol Sci. 1999 Feb;47(2):181-6. Pubmed

5. Multidrug resistance-associated protein 6

Actions: substrate

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS)

UniProt ID: O95255 Link_out
Gene: ABCC6 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. Pubmed

6. Bile salt export pump

Actions: substrate

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed
  2. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. Pubmed

7. Multidrug resistance-associated protein 7

Actions: substrate

ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion

UniProt ID: Q5T3U5 Link_out
Gene: ABCC10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. Pubmed

8. ATP-binding cassette sub-family G member 2

Actions: substrate

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, van Veen HW: Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51. Epub 2003 Mar 28. Pubmed
  2. Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B: Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7. Pubmed
  3. Nakanishi T, Doyle LA, Hassel B, Wei Y, Bauer KS, Wu S, Pumplin DW, Fang HB, Ross DD: Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis. Mol Pharmacol. 2003 Dec;64(6):1452-62. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19