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Identification
NameVincristine
Accession NumberDB00541  (APRD00495)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Vincristine is an antitumor vinca alkaloid isolated from Vinca Rosea. It is marketed under several brand names, many of which have different formulations such as Marqibo (liposomal injection) and Vincasar. Vincristine is indicated for the treatment of acute leukaemia, malignant lymphoma, Hodgkin’s disease, acute erythraemia, and acute panmyelosis. vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone–marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy).

Structure
Thumb
Synonyms
22-Oxovincaleukoblastin
22-Oxovincaleukoblastine
Leurocristine
Vincristin
Vincristina
Vincristinum
External Identifiers
  • L 37231
  • NSC 67574
  • VCR
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MarqibokitTalon Therapeutics, Inc2013-01-14Not applicableUs
Oncovin Solution 1mg/mlliquid1 mgintravenousEli Lilly Canada Inc1984-12-311998-08-04Canada
Vincristine Sulfate Inj 1mg/ml USPliquid1 mgintravenousDavid Bull Laboratories (Pty) Ltd.1989-12-311999-08-10Canada
Vincristine Sulfate Inj 5mg/vial USPpowder for solution5 mgintravenousDavid Bull Laboratories (Pty) Ltd.1989-12-311996-09-10Canada
Vincristine Sulfate Injectionsolution1 mgintravenousAccord Healthcare IncNot applicableNot applicableCanada
Vincristine Sulfate Injectionsolution1 mgintravenousTeva Canada Limited1995-12-31Not applicableCanada
Vincristine Sulfate Injection USPsolution1 mgintravenousUman Pharma IncNot applicableNot applicableCanada
Vincristine Sulfate Injection USPsolution1 mgintravenousHospira Healthcare Corporation1997-08-07Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vincasar PFSinjection, solution1 mg/mLintravenousTeva Parenteral Medicines, Inc.2000-05-01Not applicableUs
Vincasar PFSinjection, solution1 mg/mLintravenousTeva Parenteral Medicines, Inc.2000-05-01Not applicableUs
Vincristine Sulfateinjection, solution1 mg/mLintravenousHospira Worldwide, Inc.1988-04-19Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AlcavixinKorea United Pharma
AlcristAlkem
CitomidCSC
CytocristinCipla
OncocristinSun
OncovinLilly
OncrivinTeva
SindovinActavis
TevacristinTeva
VincesIvax
VincrisinTeva
VincristinGedeon Richter
VincrisulSTADA
VinlonCelon
VinracineMeizler
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Vincristine Sulfate
Thumb
  • InChI Key: AQTQHPDCURKLKT-VEGNXYBXSA-N
  • Monoisotopic Mass: 922.367023274
  • Average Mass: 923.036
DBSALT000314
Categories
UNII5J49Q6B70F
CAS number57-22-7
WeightAverage: 824.9576
Monoisotopic: 824.399644032
Chemical FormulaC46H56N4O10
InChI KeyInChIKey=OGWKCGZFUXNPDA-XQKSVPLYSA-N
InChI
InChI=1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3/t28-,37+,38-,39-,42+,43-,44-,45+,46+/m1/s1
IUPAC Name
methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0⁴,¹².0⁵,¹⁰]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.0¹,⁹.0²,⁷.0¹⁶,¹⁹]nonadeca-2,4,6,13-tetraene-10-carboxylate
SMILES
[H][C@@]12N3CC[C@@]11C4=CC(=C(OC)C=C4N(C=O)[C@@]1([H])[C@](O)([[email protected]](OC(C)=O)[C@]2(CC)C=CC3)C(=O)OC)[C@]1(C[C@]2([H])CN(C[C@](O)(CC)C2)CCC2=C1NC1=CC=CC=C21)C(=O)OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as vinca alkaloids. These are alkaloids with a dimeric chemical structure composed of an indole nucleus (catharanthine), and a dihydroindole nucleus (vindoline), joined together.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassVinca alkaloids
Sub ClassNot Available
Direct ParentVinca alkaloids
Alternative Parents
Substituents
  • Vinca alkaloid skeleton
  • Carbazole
  • Indole or derivatives
  • Indole
  • Anisole
  • Aralkylamine
  • Tetrahydropyridine
  • Alkyl aryl ether
  • Benzenoid
  • N-alkylpyrrolidine
  • Piperidine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Acetate salt
  • Methyl ester
  • Tertiary carboxylic acid amide
  • Tertiary alcohol
  • Pyrrolidine
  • Pyrrole
  • Cyclic alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • 1,2-aminoalcohol
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationTreatment of acute lymphocytic leukemia (ALL), Hodgkin lymphoma, non-Hodgkin lymphomas, Wilms' tumor, neuroblastoma, rhabdomyosarcoma. Liposomal vincristine is indicated for the treatment of relapsed Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL).
PharmacodynamicsVincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.
Mechanism of actionThe antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.
Related Articles
AbsorptionNot Available
Volume of distribution

Within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound.

Protein binding~75%
Metabolism

Hepatic. Cytochrome P450 isoenzymes of the CYP3A subfamily facilitate the metabolism of vincristine.

Route of eliminationThe liver is the major excretory organ in humans and animals. 80% of an injected dose of vincristine sulfate is excreted via feces. 10 - 20% is excreted via urine.
Half lifeWhen intravenously injected into cancer patients, a triphasic serum decay patten was observed. The initial, middle, and terminal half-lives are 5 minutes, 2.3 hours, 85 hours respectively. The range of the terminal half-life is humans is 19 - 155 hours.
ClearanceNot Available
ToxicityIVN-RAT LD50 1300 mg/kg; IPR-MUS LD50 5.2 mg/kg. Marqibo® must only be administered IV because it is fatal if administered by other routes. Marqibo® also has different dosing than vincristine sulphate injection, so attention is needed to prevent overdoses. The most clinically significant adverse effect of vincristine is neurotoxicity.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Vincristine Action PathwayDrug actionSMP00437
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9738
Blood Brain Barrier-0.9514
Caco-2 permeable+0.6262
P-glycoprotein substrateSubstrate0.9027
P-glycoprotein inhibitor IInhibitor0.6573
P-glycoprotein inhibitor IIInhibitor0.6919
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.8071
CYP450 2D6 substrateNon-substrate0.9138
CYP450 3A4 substrateSubstrate0.7666
CYP450 1A2 substrateNon-inhibitor0.9203
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.7491
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8574
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8938
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9324 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9699
hERG inhibition (predictor II)Inhibitor0.5265
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Teva parenteral medicines inc
  • Bristol myers squibb
  • Abic ltd
  • Abraxis pharmaceutical products
  • App pharmaceuticals llc
  • Hospira inc
Packagers
Dosage forms
FormRouteStrength
Kit
Liquidintravenous1 mg
Injection, solutionintravenous1 mg/mL
Powder for solutionintravenous5 mg
Solutionintravenous1 mg
Prices
Unit descriptionCostUnit
Vincristine 2 mg/2 ml vial18.06USD ml
Oncovite tablet0.19USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6723338 No2000-03-312020-03-31Us
US7247316 No2000-09-252020-09-25Us
US7887836 No2000-03-312020-03-31Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point220 °CPhysProp
logP2.82HANSCH,C ET AL. (1995)
pKa5MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.03 mg/mLALOGPS
logP3.36ALOGPS
logP3.13ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)10.85ChemAxon
pKa (Strongest Basic)8.66ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area171.17 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity221.48 m3·mol-1ChemAxon
Polarizability88.59 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Homer L. Pearce, “Method of preparing vincristine.” U.S. Patent US4303584, issued November, 1967.

US4303584
General References
  1. Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD: Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996 Apr 1;77(7):1356-62. [PubMed:8608515 ]
  2. Qweider M, Gilsbach JM, Rohde V: Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report. J Neurosurg Spine. 2007 Mar;6(3):280-3. [PubMed:17355029 ]
  3. JOHNSON IS, ARMSTRONG JG, GORMAN M, BURNETT JP Jr: THE VINCA ALKALOIDS: A NEW CLASS OF ONCOLYTIC AGENTS. Cancer Res. 1963 Sep;23:1390-427. [PubMed:14070392 ]
  4. Gidding CE, Kellie SJ, Kamps WA, de Graaf SS: Vincristine revisited. Crit Rev Oncol Hematol. 1999 Feb;29(3):267-87. [PubMed:10226730 ]
External Links
ATC CodesL01CA02
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelDownload (362 KB)
MSDSDownload (90.9 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Vincristine can be increased when it is combined with Abiraterone.
AmiodaroneThe serum concentration of Vincristine can be increased when it is combined with Amiodarone.
AprepitantThe serum concentration of Vincristine can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Vincristine can be increased when it is combined with Atazanavir.
AtorvastatinThe serum concentration of Vincristine can be increased when it is combined with Atorvastatin.
AzithromycinThe serum concentration of Vincristine can be increased when it is combined with Azithromycin.
BexaroteneThe serum concentration of Vincristine can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Vincristine can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Vincristine can be decreased when it is combined with Bosentan.
CarbamazepineThe serum concentration of Vincristine can be decreased when it is combined with Carbamazepine.
CarvedilolThe serum concentration of Vincristine can be increased when it is combined with Carvedilol.
CeritinibThe serum concentration of Vincristine can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Vincristine can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Vincristine can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Vincristine can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Vincristine can be increased when it is combined with Crizotinib.
CyclosporineThe serum concentration of Vincristine can be increased when it is combined with Cyclosporine.
DabrafenibThe serum concentration of Vincristine can be decreased when it is combined with Dabrafenib.
DaclatasvirThe serum concentration of Vincristine can be increased when it is combined with Daclatasvir.
DarunavirThe serum concentration of Vincristine can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Vincristine can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Vincristine can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Vincristine.
DexamethasoneThe serum concentration of Vincristine can be decreased when it is combined with Dexamethasone.
DipyridamoleThe serum concentration of Vincristine can be increased when it is combined with Dipyridamole.
DronedaroneThe serum concentration of Vincristine can be increased when it is combined with Dronedarone.
EliglustatThe serum concentration of Vincristine can be increased when it is combined with Eliglustat.
EnzalutamideThe serum concentration of Vincristine can be decreased when it is combined with Enzalutamide.
ErythromycinThe serum concentration of Vincristine can be increased when it is combined with Erythromycin.
FlibanserinThe serum concentration of Vincristine can be increased when it is combined with Flibanserin.
FluconazoleThe metabolism of Vincristine can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Vincristine can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Vincristine can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Vincristine can be increased when it is combined with Fusidic Acid.
IbrutinibThe serum concentration of Vincristine can be increased when it is combined with Ibrutinib.
IdelalisibThe serum concentration of Vincristine can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Vincristine can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Vincristine can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Vincristine can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Vincristine can be increased when it is combined with Ketoconazole.
LapatinibThe serum concentration of Vincristine can be increased when it is combined with Lapatinib.
LedipasvirThe serum concentration of Vincristine can be increased when it is combined with Ledipasvir.
LeflunomideThe risk or severity of adverse effects can be increased when Vincristine is combined with Leflunomide.
LomitapideThe serum concentration of Vincristine can be increased when it is combined with Lomitapide.
LopinavirThe serum concentration of Vincristine can be increased when it is combined with Lopinavir.
LuliconazoleThe serum concentration of Vincristine can be increased when it is combined with Luliconazole.
MefloquineThe serum concentration of Vincristine can be increased when it is combined with Mefloquine.
MifepristoneThe serum concentration of Vincristine can be increased when it is combined with Mifepristone.
MirabegronThe serum concentration of Vincristine can be increased when it is combined with Mirabegron.
MitomycinThe risk or severity of adverse effects can be increased when Vincristine is combined with Mitomycin.
MitotaneThe serum concentration of Vincristine can be decreased when it is combined with Mitotane.
NatalizumabThe risk or severity of adverse effects can be increased when Vincristine is combined with Natalizumab.
NefazodoneThe serum concentration of Vincristine can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Vincristine can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Vincristine can be increased when it is combined with Netupitant.
NicardipineThe serum concentration of Vincristine can be increased when it is combined with Nicardipine.
NifedipineThe serum concentration of Vincristine can be increased when it is combined with Nifedipine.
NilotinibThe serum concentration of Vincristine can be increased when it is combined with Nilotinib.
PalbociclibThe serum concentration of Vincristine can be increased when it is combined with Palbociclib.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Vincristine.
PhenobarbitalThe serum concentration of Vincristine can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Vincristine can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Vincristine.
PosaconazoleThe serum concentration of Vincristine can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Vincristine can be decreased when it is combined with Primidone.
ProgesteroneThe serum concentration of Vincristine can be increased when it is combined with Progesterone.
PropranololThe serum concentration of Vincristine can be increased when it is combined with Propranolol.
QuinidineThe serum concentration of Vincristine can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Vincristine can be increased when it is combined with Quinine.
RanolazineThe serum concentration of Vincristine can be increased when it is combined with Ranolazine.
ReserpineThe serum concentration of Vincristine can be increased when it is combined with Reserpine.
RifabutinThe serum concentration of Vincristine can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Vincristine can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Vincristine can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Vincristine can be increased when it is combined with Ritonavir.
RoflumilastRoflumilast may increase the immunosuppressive activities of Vincristine.
RolapitantThe serum concentration of Vincristine can be increased when it is combined with Rolapitant.
SaquinavirThe serum concentration of Vincristine can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Vincristine can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Vincristine can be increased when it is combined with Simeprevir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Vincristine.
SofosbuvirThe serum concentration of Vincristine can be increased when it is combined with Sofosbuvir.
SpiramycinThe serum concentration of Vincristine can be increased when it is combined with Spiramycin.
St. John's WortThe serum concentration of Vincristine can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Vincristine can be increased when it is combined with Stiripentol.
SulfisoxazoleThe serum concentration of Vincristine can be increased when it is combined with Sulfisoxazole.
SunitinibThe serum concentration of Vincristine can be increased when it is combined with Sunitinib.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vincristine.
TamoxifenThe serum concentration of Vincristine can be increased when it is combined with Tamoxifen.
TelaprevirThe serum concentration of Vincristine can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Vincristine can be increased when it is combined with Telithromycin.
TeniposideTeniposide may increase the neurotoxic activities of Vincristine.
TesmilifeneThe serum concentration of Vincristine can be decreased when it is combined with Tesmilifene.
TipranavirThe serum concentration of Vincristine can be decreased when it is combined with Tipranavir.
TocilizumabThe serum concentration of Vincristine can be decreased when it is combined with Tocilizumab.
TofacitinibVincristine may increase the immunosuppressive activities of Tofacitinib.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Vincristine.
TrastuzumabTrastuzumab may increase the neutropenic activities of Vincristine.
VandetanibThe serum concentration of Vincristine can be increased when it is combined with Vandetanib.
VemurafenibThe serum concentration of Vincristine can be increased when it is combined with Vemurafenib.
VerapamilThe serum concentration of Vincristine can be increased when it is combined with Verapamil.
VinblastineThe serum concentration of Vincristine can be decreased when it is combined with Vinblastine.
VoriconazoleThe serum concentration of Vincristine can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ubiquitin protein ligase binding
Specific Function:
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.
Gene Name:
TUBB
Uniprot ID:
P07437
Molecular Weight:
49670.515 Da
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:17139284 ]
  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:17016423 ]
  3. Kurtzberg LS, Roth SD, Bagley RG, Rouleau C, Yao M, Crawford JL, Krumbholz RD, Schmid SM, Teicher BA: Bone marrow CFU-GM and human tumor xenograft efficacy of three tubulin binding agents. Cancer Chemother Pharmacol. 2009 Oct;64(5):1029-38. doi: 10.1007/s00280-009-0959-z. Epub 2009 Mar 10. [PubMed:19277662 ]
  4. Gan PP, McCarroll JA, Po'uha ST, Kamath K, Jordan MA, Kavallaris M: Microtubule dynamics, mitotic arrest, and apoptosis: drug-induced differential effects of betaIII-tubulin. Mol Cancer Ther. 2010 May;9(5):1339-48. doi: 10.1158/1535-7163.MCT-09-0679. Epub 2010 May 4. [PubMed:20442307 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Structural constituent of cytoskeleton
Specific Function:
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.
Gene Name:
TUBA4A
Uniprot ID:
P68366
Molecular Weight:
49923.995 Da
References
  1. Yasui M, Koyama N, Koizumi T, Senda-Murata K, Takashima Y, Hayashi M, Sugimoto K, Honma M: Live cell imaging of micronucleus formation and development. Mutat Res. 2010 Oct 13;692(1-2):12-8. doi: 10.1016/j.mrfmmm.2010.07.009. Epub 2010 Aug 5. [PubMed:20691709 ]
  2. Gan PP, McCarroll JA, Po'uha ST, Kamath K, Jordan MA, Kavallaris M: Microtubule dynamics, mitotic arrest, and apoptosis: drug-induced differential effects of betaIII-tubulin. Mol Cancer Ther. 2010 May;9(5):1339-48. doi: 10.1158/1535-7163.MCT-09-0679. Epub 2010 May 4. [PubMed:20442307 ]
  3. Vilpo JA, Koski T, Vilpo LM: Selective toxicity of vincristine against chronic lymphocytic leukemia cells in vitro. Eur J Haematol. 2000 Dec;65(6):370-8. [PubMed:11168494 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It 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 xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular Weight:
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitorinducer
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
References
  1. Arora A, Shukla Y: Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol. Cancer Lett. 2003 Jan 28;189(2):167-73. [PubMed:12490309 ]
  2. 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:11602674 ]
  3. 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:12134945 ]
  4. Doppenschmitt S, Langguth P, Regardh CG, Andersson TB, Hilgendorf C, Spahn-Langguth H: Characterization of binding properties to human P-glycoprotein: development of a [3H]verapamil radioligand-binding assay. J Pharmacol Exp Ther. 1999 Jan;288(1):348-57. [PubMed:9862789 ]
  5. 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:14985103 ]
  6. 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:12608535 ]
  7. 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:10617675 ]
  8. 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:15231674 ]
  9. 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. doi: 10.1007/s00280-008-0906-4. Epub 2009 Jan 4. [PubMed:19123050 ]
  10. 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. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [PubMed:19427995 ]
  11. 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. doi: 10.1111/j.1349-7006.2009.01213.x. Epub 2009 May 12. [PubMed:19493273 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Organic anion transmembrane transporter activity
Specific Function:
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity).
Gene Name:
ABCC3
Uniprot ID:
O15438
Molecular Weight:
169341.14 Da
References
  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [PubMed:11585759 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Toxin transporter activity
Specific Function:
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name:
SLC22A3
Uniprot ID:
O75751
Molecular Weight:
61279.485 Da
References
  1. Shnitsar V, Eckardt R, Gupta S, Grottker J, Muller GA, Koepsell H, Burckhardt G, Hagos Y: Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res. 2009 Feb 15;69(4):1494-501. doi: 10.1158/0008-5472.CAN-08-2483. Epub 2009 Feb 3. [PubMed:19190342 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Transporter activity
Specific Function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
References
  1. 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:8621644 ]
  2. 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:12657726 ]
  3. 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:12867490 ]
  4. Sumizawa T, Chen ZS, Chuman Y, Seto K, Furukawa T, Haraguchi M, Tani A, Shudo N, Akiyama SI: Reversal of multidrug resistance-associated protein-mediated drug resistance by the pyridine analog PAK-104P. Mol Pharmacol. 1997 Mar;51(3):399-405. [PubMed:9058594 ]
  5. 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:10188979 ]
  6. 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:9281595 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name:
ABCC10
Uniprot ID:
Q5T3U5
Molecular Weight:
161627.375 Da
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:12527806 ]
  2. 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. doi: 10.1158/0008-5472.CAN-08-1420. [PubMed:19118001 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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
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:12134946 ]
  2. Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS: Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun. 2003 Oct 10;310(1):222-7. [PubMed:14511674 ]
  3. Ishikawa T, Muller M, Klunemann C, Schaub T, Keppler D: ATP-dependent primary active transport of cysteinyl leukotrienes across liver canalicular membrane. Role of the ATP-dependent transport system for glutathione S-conjugates. J Biol Chem. 1990 Nov 5;265(31):19279-86. [PubMed:2172249 ]
  4. Chen ZS, Kawabe T, Ono M, Aoki S, Sumizawa T, Furukawa T, Uchiumi T, Wada M, Kuwano M, Akiyama SI: Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter. Mol Pharmacol. 1999 Dec;56(6):1219-28. [PubMed:10570049 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transporter activity
Specific Function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular Weight:
146405.83 Da
References
  1. 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:10617675 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Allen JD, Van Dort SC, Buitelaar M, van Tellingen O, Schinkel AH: Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003 Mar 15;63(6):1339-44. [PubMed:12649196 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transmembrane transporter activity
Specific Function:
Can activate specifically hydrolysis of GTP bound to RAC1 and CDC42, but not RALA. Mediates ATP-dependent transport of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin (DOX) and is the major ATP-dependent transporter of glutathione conjugates of electrophiles (GS-E) and DOX in erythrocytes. Can catalyze transport of glutathione conjugates and xenobiotics, and may contribute to the mul...
Gene Name:
RALBP1
Uniprot ID:
Q15311
Molecular Weight:
76062.86 Da
References
  1. Drake KJ, Singhal J, Yadav S, Nadkar A, Pungaliya C, Singhal SS, Awasthi S: RALBP1/RLIP76 mediates multidrug resistance. Int J Oncol. 2007 Jan;30(1):139-44. [PubMed:17143522 ]
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Drug created on June 13, 2005 07:24 / Updated on May 30, 2016 02:09