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Identification
Name Paclitaxel
Accession Number DB01229 (APRD00259, DB05261, DB05927)
Type small molecule
Groups approved
Description

A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS brevifolia. It stabilizes microtubules in their polymerized form leading to cell death. [PubChem] ABI-007 (Abraxane) is the latest attempt to improve upon paclitaxel, one of the leading chemotherapy treatments. Both drugs contain the same active agent, but Abraxane is delivered by a nanoparticle technology that binds to albumin, a natural protein, rather than the toxic solvent known as Cremophor. It is thought that delivering paclitaxel with this technology will cause fewer hypersensitivity reactions and possibly lead to greater drug uptake in tumors.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
7-epi-Paclitaxel
7-epi-Taxol
7-Epipaclitaxel
7-Epitaxol
ABI-007
Salts Not Available
Brand names
Name Company
Abraxane Abraxis Bioscience
Epitaxol
Onxol
Paxceed
Paxene
Taxol
Taxol A
Vascular Wrap
Xorane
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Tubulin Modulators
CAS number 33069-62-4
Weight Average: 853.9061
Monoisotopic: 853.330955345
Chemical Formula C47H51NO14
InChI Key InChIKey=RCINICONZNJXQF-MZXODVADSA-N
InChI
InChI=1S/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)49)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37+,38-,40-,45+,46-,47+/m0/s1
Plain Text
IUPAC Name
(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
SMILES
[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Taxanes
Substructures
  • Taxanes
  • Carbonyl Compounds
  • Carboxylic Acids and Derivatives
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Amino Ketones
  • Short-chain Hydroxy Acids
  • Cyclobutane and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Cyclohexenes and Derivatives
  • Cyclooctane and Derivatives
  • Benzamides
  • Ketones
Pharmacology
Indication Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast.
Pharmacodynamics Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Mechanism of action Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
Absorption I.V injected
Volume of distribution
  • 227 to 688 L/m2
Protein binding 89%-98%
Metabolism Hepatic. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4.
Route of elimination In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered in the urine.
Half life Average distribution half-life of 0.34 hours and an average elimination half-life of 5.8 hours.
Clearance
  • 21.7 L/h/m2 [Dose 135 mg/m2, infusion duration 24 h]
  • 23.8 L/h/m2 [Dose 175 mg/m2, infusion duration 24 h]
  • 7 L/h/m2 [Dose 135 mg/m2, infusion duration 3 h]
  • 12.2 L/h/m2 [Dose 175 mg/m2, infusion duration 3 h]
Toxicity Rat (ipr) LD50=32530 µg/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00434 Paclitaxel Pathway SMP00434
Pharmacoeconomics
Manufacturers
  • Abraxis bioscience llc
  • Accord healthcare inc usa
  • Actavis totowa llc
  • Bedford laboratories div ben venue laboratories inc
  • Ebewe pharma ges mbh nfg kg
  • Fresenius kabi oncology plc
  • Hospira inc
  • Mylan pharmaceuticals inc
  • Pliva lachema as
  • Teva parenteral medicines inc
  • Bristol myers squibb co pharmaceutical research institute
Packagers
Dosage forms
Form Route Strength
Powder, for suspension Intravenous
Solution Intravenous
Prices
Unit description Cost Unit
Abraxane 100 mg vial 1119.6 USD vial
Taxol 30 mg/5 ml vial 35.06 USD ml
Onxol 30 mg/5 ml vial 34.54 USD ml
Onxol 300 mg/50 ml vial 34.54 USD ml
Paclitaxel 300 mg/50 ml vial 5.31 USD ml
Paclitaxel 100 mg/16.7 ml vial 4.45 USD ml
Paclitaxel 30 mg/5 ml vial 3.54 USD ml
Paclitaxel 150 mg/25 ml vial 3.36 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5498421 1993-03-12 2013-03-12
United States 5439686 1993-02-22 2013-02-22
Canada 2155947 2007-08-21 2014-02-22
Canada 2086874 1998-09-01 2013-01-07
Properties
State solid
Experimental Properties
Property Value Source
melting point 213-216 °C Not Available
water solubility Insoluble Not Available
logP 3 Not Available
Predicted Properties
Property Value Source
water solubility 5.56e-03 g/l ALOGPS
logP 3.2 ALOGPS
logP 3.54 ChemAxon
logS -5.2 ALOGPS
pKa (strongest acidic) 10.36 ChemAxon
pKa (strongest basic) -1 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 10 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 221.29 ChemAxon
rotatable bond count 14 ChemAxon
refractivity 218.29 ChemAxon
polarizability 87.17 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Wall ME, Wani MC: Camptothecin and taxol: discovery to clinic—thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Res. 1995 Feb 15;55(4):753-60. Pubmed
  2. Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT: Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc. 1971 May 5;93(9):2325-7. Pubmed
  3. Fuchs DA, Johnson RK: Cytologic evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison. Cancer Treat Rep. 1978 Aug;62(8):1219-22. Pubmed
  4. Saville MW, Lietzau J, Pluda JM, Feuerstein I, Odom J, Wilson WH, Humphrey RW, Feigal E, Steinberg SM, Broder S, et al.: Treatment of HIV-associated Kaposi’s sarcoma with paclitaxel. Lancet. 1995 Jul 1;346(8966):26-8. Pubmed
  5. ABI 007. Drugs R D. 2004;5(3):155-9. Pubmed
  6. Gaitanis A, Staal S: Liposomal doxorubicin and nab-paclitaxel: nanoparticle cancer chemotherapy in current clinical use. Methods Mol Biol. 2010;624:385-92. Pubmed
External Links
Resource Link
KEGG Drug D00491 Link_out
KEGG Compound C07394 Link_out
PubChem Compound 36314 Link_out
PubChem Substance 46506910 Link_out
ChemSpider 33395 Link_out
ChEBI 7887 Link_out
ChEMBL 7887 Link_out
Therapeutic Targets Database DNC001411 Link_out
PharmGKB PA450761 Link_out
IUPHAR 2770 Link_out
Guide to Pharmacology 2770 Link_out
Drug Product Database 2244372 Link_out
RxList http://www.rxlist.com/cgi/generic/paclitaxel.htm Link_out
Drugs.com http://www.drugs.com/cdi/paclitaxel.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Paclitaxel Link_out
ATC Codes
  • L01CD01
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label show (328 KB)
MSDS show (74 KB)
Interactions
Drug Interactions
Drug Interaction
Aprepitant Aprepitant may change levels of the chemotherapy agent, paclitaxel.
Carboplatin Platinum derivatives such as carboplatin may enhance the myelosuppressive effect of taxane derivatives such as paclitaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity. Administering the taxane derivative before the platinum derivative seems prudent.
Cisplatin Cisplatin increases the effect and toxicity of paclitaxel
Gemcitabine Paclitaxel increases the effect/toxicity of gemcitabine
Pazopanib Pazopanib increases exposure of paclitaxel
Quinupristin This combination presents an increased risk of toxicity
Telithromycin Telithromycin may reduce clearance of Paclitaxel. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Paclitaxel if Telithromycin is initiated, discontinued or dose changed.
Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Paclitaxel. Consider alternate therapy or monitor for changes in Paclitaxel therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Concomitant therapy may also increase Trastuzumab serum concentration and decrease Paclitaxel serum concentrations. Monitor closely for adverse events and therapeutic response.
Valrubicin The taxane derivative, Paclitaxel, may increase Valrubicin toxicity. Consider alternate therapy or monitor for toxic effects.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of paclitaxel by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of paclitaxel if voriconazole is initiated, discontinued or dose changed.
Food Interactions Not Available
Targets

1. Tubulin beta-1 chain

Pharmacological action: yes
Actions: inhibitor

Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha-chain

Organism class: human
UniProt ID: Q9H4B7 Link_out
Gene: TUBB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Cheung CH, Chen HH, Kuo CC, Chang CY, Coumar MS, Hsieh HP, Chang JY: Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers. Mol Cancer. 2009 Jul 3;8:43. Pubmed
  4. Horwitz SB: Mechanism of action of taxol. Trends Pharmacol Sci. 1992 Apr;13(4):134-6. Pubmed
  5. Kovacs P, Csaba G, Pallinger E, Czaker R: Effects of taxol treatment on the microtubular system and mitochondria of Tetrahymena. Cell Biol Int. 2007 Jul;31(7):724-32. Epub 2007 Jan 14. Pubmed

2. Apoptosis regulator Bcl-2

Pharmacological action: yes
Actions: inhibitor

Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1)

Organism class: human
UniProt ID: P10415 Link_out
Gene: BCL2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gan Y, Wientjes MG, Au JL: Expression of basic fibroblast growth factor correlates with resistance to paclitaxel in human patient tumors. Pharm Res. 2006 Jun;23(6):1324-31. Epub 2006 Jun 8. Pubmed
  2. Thomadaki H, Talieri M, Scorilas A: Treatment of MCF-7 cells with taxol and etoposide induces distinct alterations in the expression of apoptosis-related genes BCL2, BCL2L12, BAX, CASPASE-9 and FAS. Biol Chem. 2006 Aug;387(8):1081-6. Pubmed
  3. Yoshino T, Shiina H, Urakami S, Kikuno N, Yoneda T, Shigeno K, Igawa M: Bcl-2 expression as a predictive marker of hormone-refractory prostate cancer treated with taxane-based chemotherapy. Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6116-24. Pubmed
  4. Matsuyoshi S, Shimada K, Nakamura M, Ishida E, Konishi N: Bcl-2 phosphorylation has pathological significance in human breast cancer. Pathobiology. 2006;73(4):205-12. Pubmed
  5. Zhang X, Wang Q, Ling MT, Wong YC, Leung SC, Wang X: Anti-apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells. Int J Cancer. 2007 May 1;120(9):1891-8. Pubmed
Enzymes

1. Cytochrome P450 2C9

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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
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: 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: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A7

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: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 2C8

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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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 3A4

Actions: substrate, inhibitor, 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 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. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Cytochrome P450 19A1

Actions: inhibitor

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

UniProt ID: P11511 Link_out
Gene: CYP19A1 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

7. 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
Transporters

1. Bile salt export pump

Actions: substrate, inhibitor

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

2. Multidrug resistance protein 1

Actions: substrate, inhibitor

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. 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
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  3. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. Pubmed
  4. Jang SH, Wientjes MG, Au JL: Kinetics of P-glycoprotein-mediated efflux of paclitaxel. J Pharmacol Exp Ther. 2001 Sep;298(3):1236-42. Pubmed
  5. Li D, Jang SH, Kim J, Wientjes MG, Au JL: Enhanced drug-induced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res. 2003 Jan;20(1):45-50. Pubmed
  6. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed
  7. Kim S, Kim SS, Bang YJ, Kim SJ, Lee BJ: In vitro activities of native and designed peptide antibiotics against drug sensitive and resistant tumor cell lines. Peptides. 2003 Jul;24(7):945-53. Pubmed
  8. Walle UK, Walle T: Taxol transport by human intestinal epithelial Caco-2 cells. Drug Metab Dispos. 1998 Apr;26(4):343-6. Pubmed
  9. 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
  10. Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. Pubmed
  11. Kuo CC, Hsieh HP, Pan WY, Chen CP, Liou JP, Lee SJ, Chang YL, Chen LT, Chen CT, Chang JY: BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res. 2004 Jul 1;64(13):4621-8. Pubmed
  12. Li YC, Fung KP, Kwok TT, Lee CY, Suen YK, Kong SK: Mitochondria-targeting drug oligomycin blocked P-glycoprotein activity and triggered apoptosis in doxorubicin-resistant HepG2 cells. Chemotherapy. 2004 Jun;50(2):55-62. Pubmed
  13. Kwak JO, Lee SH, Lee GS, Kim MS, Ahn YG, Lee JH, Kim SW, Kim KH, Lee MG: Selective inhibition of MDR1 (ABCB1) by HM30181 increases oral bioavailability and therapeutic efficacy of paclitaxel. Eur J Pharmacol. 2010 Feb 10;627(1-3):92-8. Epub 2009 Nov 10. Pubmed
  14. Woodahl EL, Crouthamel MH, Bui T, Shen DD, Ho RJ: MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8. Epub 2009 Jan 4. Pubmed
  15. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. Epub 2009 Apr 11. Pubmed
  16. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. Epub 2009 May 12. Pubmed

3. Multidrug resistance-associated protein 1

Actions: 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. 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

4. Multidrug resistance-associated protein 7

Actions: substrate, inhibitor

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. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. Pubmed
  2. Zhou Y, Hopper-Borge E, Shen T, Huang XC, Shi Z, Kuang YH, Furukawa T, Akiyama S, Peng XX, Ashby CR Jr, Chen X, Kruh GD, Chen ZS: Cepharanthine is a potent reversal agent for MRP7-mediated multidrug resistance. Biochem Pharmacol. 2009 Mar 15;77(6):993-1001. Epub 2008 Dec 25. Pubmed
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Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:20