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Identification
NamePaclitaxel
Accession NumberDB01229  (APRD00259, DB05261, DB05927)
Typesmall molecule
Groupsapproved
Description

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel.
When it was developed commercially by Bristol-Myers Squibb (BMS), the generic name was changed to paclitaxel and the BMS compound is sold under the trademark Taxol. In this formulation, paclitaxel is dissolved in Kolliphor EL and ethanol, as a delivery agent. A newer formulation, in which paclitaxel is bound to albumin, is sold under the trademark Abraxane. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
TaxolNot AvailableNot Available
Taxol ANot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AbraxaneAbraxis Bioscience
OnxolNot Available
PaxceedNot Available
PaxeneNot Available
TaxolNot Available
Brand mixturesNot Available
Categories
CAS number33069-62-4
WeightAverage: 853.9061
Monoisotopic: 853.330955345
Chemical FormulaC47H51NO14
InChI KeyInChIKey=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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassPrenol Lipids
SubclassDiterpenes
Direct parentTaxanes and 11(15->1)Abeotaxanes
Alternative parentsGermacrane Sesquiterpenes; Phenylpyruvic Acid Derivatives; Beta Amino Acids and Derivatives; Benzoic Acid Esters; Phenylpropylamines; Benzamides; Benzylethers; Benzoyl Derivatives; Cyclohexanols; Dicarboxylic Acids and Derivatives; Tertiary Alcohols; Ketones; Cyclic Alcohols and Derivatives; Oxetanes; Carboxylic Acid Esters; Secondary Carboxylic Acid Amides; Dialkyl Ethers; Carboxylic Acids; Enolates; Polyamines; Aldehydes
Substituentsgermacrane sesquiterpene; phenylpyruvate; beta amino acid or derivative; benzoate ester; phenylpropylamine; benzylether; benzamide; benzoic acid or derivative; benzoyl; cyclohexanol; benzene; dicarboxylic acid derivative; tertiary alcohol; cyclic alcohol; oxetane; carboxylic acid ester; ketone; carboxamide group; secondary alcohol; secondary carboxylic acid amide; polyamine; carboxylic acid; dialkyl ether; carboxylic acid derivative; enolate; ether; amine; carbonyl group; alcohol; organonitrogen compound; aldehyde
Classification descriptionThis compound belongs to the taxanes and 11(15->1)abeotaxanes. These are diterpenes whose structure is based on the taxane or 11(15->1)abeaotaxane skeleton, which is characterized by a 6-8-6 tricyclic ring system.
Pharmacology
IndicationUsed in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast. Abraxane® is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer.
PharmacodynamicsPaclitaxel 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 actionPaclitaxel 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.
AbsorptionWhen a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the maximum plasma concentration (Cmax) is 195 ng/mL, while the AUC is 6300 ng•h/mL.
Volume of distribution
  • 227 to 688 L/m^2 [apparent volume of distribution at steady-state, 24 hour infusion]
Protein binding89%-98% bound to plasma protein. The presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel.
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.

SubstrateEnzymesProduct
Paclitaxel
    3'-p-hydroxypaclitaxelDetails
    Paclitaxel
      6a-hydrox-ypaclitaxelDetails
      Paclitaxel
        6a, 3'-p-dihydroxypaclitaxelDetails
        Route of eliminationIn 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 lifeWhen a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the elimination half=life is 52.7 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]
        ToxicityRat (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
        PathwayCategorySMPDB ID
        Paclitaxel Action PathwayDrug actionSMP00434
        SNP Mediated EffectsNot Available
        SNP Mediated Adverse Drug ReactionsNot Available
        ADMET
        Predicted ADMET features
        Property Value Probability
        Human Intestinal Absorption + 0.914
        Blood Brain Barrier - 0.9748
        Caco-2 permeable - 0.8957
        P-glycoprotein substrate Substrate 0.8345
        P-glycoprotein inhibitor I Inhibitor 0.5509
        P-glycoprotein inhibitor II Non-inhibitor 0.7309
        Renal organic cation transporter Non-inhibitor 0.9349
        CYP450 2C9 substrate Non-substrate 0.837
        CYP450 2D6 substrate Non-substrate 0.9116
        CYP450 3A4 substrate Substrate 0.7278
        CYP450 1A2 substrate Non-inhibitor 0.9045
        CYP450 2C9 substrate Non-inhibitor 0.9071
        CYP450 2D6 substrate Non-inhibitor 0.9231
        CYP450 2C19 substrate Non-inhibitor 0.9025
        CYP450 3A4 substrate Non-inhibitor 0.8309
        CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8937
        Ames test Non AMES toxic 0.9132
        Carcinogenicity Non-carcinogens 0.9158
        Biodegradation Not ready biodegradable 0.9491
        Rat acute toxicity 2.4391 LD50, mol/kg Not applicable
        hERG inhibition (predictor I) Weak inhibitor 0.9978
        hERG inhibition (predictor II) Non-inhibitor 0.7982
        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
        FormRouteStrength
        ConcentrateIntravenous100 mg/16.7 mL; 30 mg/5 mL; 150 mg/25 mL; 300 mg/50 mL
        Prices
        Unit descriptionCostUnit
        Abraxane 100 mg vial1119.6USDvial
        Taxol 30 mg/5 ml vial35.06USDml
        Onxol 30 mg/5 ml vial34.54USDml
        Onxol 300 mg/50 ml vial34.54USDml
        Paclitaxel 300 mg/50 ml vial5.31USDml
        Paclitaxel 100 mg/16.7 ml vial4.45USDml
        Paclitaxel 30 mg/5 ml vial3.54USDml
        Paclitaxel 150 mg/25 ml vial3.36USDml
        DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
        Patents
        CountryPatent NumberApprovedExpires (estimated)
        United States54984211993-03-122013-03-12
        United States54396861993-02-222013-02-22
        Canada21559472007-08-212014-02-22
        Canada20868741998-09-012013-01-07
        Properties
        Statesolid
        Experimental Properties
        PropertyValueSource
        melting point216-217 °CFDA label
        water solubilityInsolubleFDA label
        logP3Not Available
        Predicted Properties
        PropertyValueSource
        water solubility5.56e-03 g/lALOGPS
        logP3.2ALOGPS
        logP3.54ChemAxon
        logS-5.2ALOGPS
        pKa (strongest acidic)10.36ChemAxon
        pKa (strongest basic)-1ChemAxon
        physiological charge0ChemAxon
        hydrogen acceptor count10ChemAxon
        hydrogen donor count4ChemAxon
        polar surface area221.29ChemAxon
        rotatable bond count14ChemAxon
        refractivity218.29ChemAxon
        polarizability87.17ChemAxon
        number of rings7ChemAxon
        bioavailability0ChemAxon
        rule of fiveNoChemAxon
        Ghose filterNoChemAxon
        Veber's ruleNoChemAxon
        MDDR-like ruleYesChemAxon
        Spectra
        SpectraNot Available
        References
        Synthesis Reference

        Hendricus B. A. de Bont, Ruben G. G. Leenders, Johan W. Scheeren, Hidde J. Haisma, Dick de Vos, “Paclitaxel prodrugs, method for preparation as well as their use in selective chemotherapy.” U.S. Patent US5760072, issued September, 1989.

        US5760072
        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
        ResourceLink
        KEGG DrugD00491
        KEGG CompoundC07394
        PubChem Compound36314
        PubChem Substance46506910
        ChemSpider33395
        ChEBI7887
        ChEMBLCHEMBL428647
        Therapeutic Targets DatabaseDNC001411
        PharmGKBPA450761
        IUPHAR2770
        Guide to Pharmacology2770
        Drug Product Database2244372
        RxListhttp://www.rxlist.com/cgi/generic/paclitaxel.htm
        Drugs.comhttp://www.drugs.com/cdi/paclitaxel.html
        WikipediaPaclitaxel
        ATC CodesL01CD01
        AHFS Codes
        • 10:00.00
        PDB EntriesNot Available
        FDA labelshow(220 KB)
        MSDSshow(74 KB)
        Interactions
        Drug Interactions
        Drug
        AprepitantAprepitant may change levels of the chemotherapy agent, paclitaxel.
        AxitinibAvoid combination due to potential for decrease in serum concentration of axitinib.
        CarboplatinPlatinum 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.
        CisplatinCisplatin increases the effect and toxicity of paclitaxel
        ClozapineAvoid combination due to the potential enhancement of agranulocytosis by clozapine.
        ConivaptanAvoid combination because it will likely increase the serum concentration of CYP3A4 substrates.
        EtravirinePaclitaxel, when used concomitantly with NNRTIs, may experience an increase in serum concentration. It is recommended to monitor for paclitaxel toxicity.
        GemcitabinePaclitaxel increases the effect/toxicity of gemcitabine
        NatalizumabAvoid combination due to the increased risk of infection.
        PazopanibPazopanib increases exposure of paclitaxel
        PimecrolimusAvoid combination due to the enhancement of adverse effects of immunosuppressants.
        QuinupristinThis combination presents an increased risk of toxicity
        St. John's WortAvoid combination due to potential decrease in serum concentration of paclitaxel.
        TacrolimusAvoid combination of topical tacrolimus due to the potential enhancement of adverse effects of immunosuppressants.
        TelithromycinTelithromycin 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.
        TolbutamideTolbutamide, 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.
        TrastuzumabTrastuzumab 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.
        ValrubicinThe taxane derivative, Paclitaxel, may increase Valrubicin toxicity. Consider alternate therapy or monitor for toxic effects.
        VoriconazoleVoriconazole, 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
        • Avoid echinacea.
        • Avoid grapefruit and grapefruit juice due to potential increase of paclitaxel.

        1. Tubulin beta-1 chain

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Tubulin beta-1 chain Q9H4B7 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Apoptosis regulator Bcl-2 P10415 Details

        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

        3. Nuclear receptor subfamily 1 group I member 2

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: inducer

        Components

        Name UniProt ID Details
        Nuclear receptor subfamily 1 group I member 2 O75469 Details

        References:

        1. Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. doi: 10.1007/s00280-008-0842-3. Epub 2008 Oct 7. Pubmed

        4. Microtubule-associated protein 4

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Components

        Name UniProt ID Details
        Microtubule-associated protein 4 P27816 Details

        References:

        1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. Pubmed

        5. Microtubule-associated protein 2

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Components

        Name UniProt ID Details
        Microtubule-associated protein 2 P11137 Details

        References:

        1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. Pubmed

        6. Microtubule-associated protein tau

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Components

        Name UniProt ID Details
        Microtubule-associated protein tau P10636 Details

        References:

        1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. Pubmed

        1. Cytochrome P450 2C9

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2C9 P11712 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 3A5 P20815 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 3A7 P24462 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2C8 P10632 Details

        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
        3. Yu L, Shi D, Ma L, Zhou Q, Zeng S: Influence of CYP2C8 polymorphisms on the hydroxylation metabolism of paclitaxel, repaglinide and ibuprofen enantiomers in vitro. Biopharm Drug Dispos. 2013 Jul;34(5):278-87. doi: 10.1002/bdd.1842. Epub 2013 Jun 3. Pubmed

        5. Cytochrome P450 3A4

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate inhibitor inducer

        Components

        Name UniProt ID Details
        Cytochrome P450 3A4 P08684 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Cytochrome P450 19A1 P11511 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Cytochrome P450 1B1 Q16678 Details

        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

        1. Bile salt export pump

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate inhibitor

        Components

        Name UniProt ID Details
        Bile salt export pump O95342 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate inhibitor

        Components

        Name UniProt ID Details
        Multidrug resistance protein 1 P08183 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Multidrug resistance-associated protein 1 P33527 Details

        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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate inhibitor

        Components

        Name UniProt ID Details
        Multidrug resistance-associated protein 7 Q5T3U5 Details

        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
        3. 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

        5. Solute carrier organic anion transporter family member 1B3

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Solute carrier organic anion transporter family member 1B3 Q9NPD5 Details

        References:

        1. Smith NF, Acharya MR, Desai N, Figg WD, Sparreboom A: Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel. Cancer Biol Ther. 2005 Aug;4(8):815-8. Pubmed

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

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

        References:

        1. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhanel M, Spruss T, Bernhardt G, Graeff C, Farber L, Gschaidmeier H, Buschauer A, Fricker G: Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest. 2002 Nov;110(9):1309-18. Pubmed

        7. Canalicular multispecific organic anion transporter 1

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Canalicular multispecific organic anion transporter 1 Q92887 Details

        References:

        1. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhanel M, Spruss T, Bernhardt G, Graeff C, Farber L, Gschaidmeier H, Buschauer A, Fricker G: Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest. 2002 Nov;110(9):1309-18. Pubmed

        Comments
        Drug created on June 13, 2005 07:24 / Updated on October 04, 2013 00:31