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Identification
NameDacarbazine
Accession NumberDB00851  (APRD00331)
TypeSmall Molecule
GroupsApproved, Investigational
Description

An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564). Dacarbazine with Oblimersen is in clinical trials for the treatment of malignant melanoma.

Structure
Thumb
Synonyms
4-(3,3-Dimethyl-1-triazeno)imidazole-5-carboxamide
4-(5)-(3,3-Dimethyl-1-triazeno)imidazole-5(4)-carboxamide
4-(Dimethyltriazeno)imidazole-5-carboxamide
5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide
5-(3,3-Dimethyltriazeno)imidazole-4-carboxamide
5-(Dimethyltriazeno)imidazole-4-carboxamide
Biocarbazine
Dacarbazin
Dacarbazina
Dacarbazine
Dacarbazinum
DIC
DTCI
Dtic-dome (tn)
DTIE
HSDB 3219
ICDMT
Imidazole Carboxamide
Imidazole-4-carboxamide, 5-(3,3-dimethyl-1-triazeno)-
NCI-C04717
NSC 45388
NSC-45388
External Identifiers
  • NSC 45 388
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dacarbazine for Injection BPpowder for solution600 mgintravenousHospira Healthcare Corporation2000-04-04Not applicableCanada
Dtic Dome Inj 200mg/vialliquid200 mgintravenousMiles Canada Inc. Pharmaceutical Division1976-12-311998-09-25Canada
Dtic-dome -pws IV 200mg/vialpowder for solution10 mgintravenousBayer Inc1996-10-102005-05-31Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dacarbazineinjection, powder, for solution200 mg/20mLintravenousTeva Parenteral Medicines, Inc.1998-08-272016-04-05Us
Dacarbazineinjection, powder, for solution10 mg/mLintravenousAPP Pharmaceuticals, LLC2001-09-072016-04-05Us
Dacarbazineinjection, powder, for solution10 mg/mLintravenousAPP Pharmaceuticals, LLC2001-09-072016-04-05Us
Dacarbazineinjection, powder, for solution10 mg/mLintravenousHospira Worldwide, Inc.2001-10-182016-04-05Us
Over the Counter ProductsNot Available
International Brands
NameCompany
DacaticOrion Corporation
DéticèneSanofi-Aventis
DeticeneSanofi-Aventis
Detimedacmedac GmbH
DTICBayer AG
DTIC-DomeBayer Schering
Brand mixturesNot Available
SaltsNot Available
Categories
UNII7GR28W0FJI
CAS number4342-03-4
WeightAverage: 182.1832
Monoisotopic: 182.091608972
Chemical FormulaC6H10N6O
InChI KeyInChIKey=FDKXTQMXEQVLRF-UHFFFAOYSA-N
InChI
InChI=1S/C6H10N6O/c1-12(2)11-10-6-4(5(7)13)8-3-9-6/h3H,1-2H3,(H2,7,13)(H,8,9)
IUPAC Name
5-(dimethyltriaz-1-en-1-yl)-1H-imidazole-4-carboxamide
SMILES
CN(C)N=NC1=C(N=CN1)C(N)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as imidazoles. These are compounds containing an imidazole ring, which is an aromatic five-member ring with two nitrogen atoms at positions 1 and 3, and three carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassImidazoles
Direct ParentImidazoles
Alternative Parents
Substituents
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Primary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of metastatic malignant melanoma. In addition, dacarbazine is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other antineoplastic agents.
PharmacodynamicsDacarbazine is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). After intravenous administration of dacarbazine, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. 1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. 1 The average cumulative excretion of unchanged DTIC in the urine is 40% of the injected dose in 6 hours. 1 DTIC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.
Mechanism of actionThe mechanism of action is not known, but appears to exert cytotoxic effects via its action as an alkylating agent. Other theories include DNA synthesis inhibition by its action as a purine analog, and interaction with SH groups. Dacarbazine is not cell cycle-phase specific.
Related Articles
AbsorptionErratic, slow and incomplete
Volume of distributionNot Available
Protein bindingLess than 5%
Metabolism

Hepatic

Route of eliminationDacarbazine is subject to renal tubular secretion rather than glomerular filtration. In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine.
Half life5 hours
ClearanceNot Available
ToxicityLD50=350mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9923
Blood Brain Barrier+0.9382
Caco-2 permeable+0.5278
P-glycoprotein substrateNon-substrate0.6608
P-glycoprotein inhibitor INon-inhibitor0.8478
P-glycoprotein inhibitor IINon-inhibitor0.9363
Renal organic cation transporterNon-inhibitor0.9125
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.579
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9496
CYP450 2D6 inhibitorNon-inhibitor0.9413
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.99
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8208
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.7624
BiodegradationNot ready biodegradable0.9879
Rat acute toxicity1.9602 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9812
hERG inhibition (predictor II)Non-inhibitor0.7856
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Abraxis pharmaceutical products
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Teva parenteral medicines inc
  • Bayer healthcare pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, for solutionintravenous10 mg/mL
Injection, powder, for solutionintravenous200 mg/20mL
Powder for solutionintravenous600 mg
Liquidintravenous200 mg
Powder for solutionintravenous10 mg
Prices
Unit descriptionCostUnit
Dacarbazine 200 mg vial22.21USD each
Dacarbazine 100 mg vial11.34USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point205 °CPhysProp
water solubility4220 mg/LNot Available
logP-0.24HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility1.36 mg/mLALOGPS
logP-0.32ALOGPS
logP-0.43ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)5.89ChemAxon
pKa (Strongest Basic)1.72ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.73 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity49.71 m3·mol-1ChemAxon
Polarizability17.78 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesL01AX04
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Dacarbazine can be increased when it is combined with Abiraterone.
BortezomibThe metabolism of Dacarbazine can be decreased when combined with Bortezomib.
CarbamazepineThe metabolism of Dacarbazine can be increased when combined with Carbamazepine.
ClozapineThe risk or severity of adverse effects can be increased when Dacarbazine is combined with Clozapine.
Cyproterone acetateThe serum concentration of Dacarbazine can be decreased when it is combined with Cyproterone acetate.
DeferasiroxThe serum concentration of Dacarbazine can be increased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Dacarbazine.
DisulfiramThe metabolism of Dacarbazine can be decreased when combined with Disulfiram.
FluvoxamineThe metabolism of Dacarbazine can be decreased when combined with Fluvoxamine.
IsoniazidThe metabolism of Dacarbazine can be decreased when combined with Isoniazid.
LeflunomideThe risk or severity of adverse effects can be increased when Dacarbazine is combined with Leflunomide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Dacarbazine.
MexiletineThe metabolism of Dacarbazine can be decreased when combined with Mexiletine.
NatalizumabThe risk or severity of adverse effects can be increased when Dacarbazine is combined with Natalizumab.
Peginterferon alfa-2bThe serum concentration of Dacarbazine can be increased when it is combined with Peginterferon alfa-2b.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Dacarbazine.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Dacarbazine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Dacarbazine.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Dacarbazine.
SorafenibThe serum concentration of Dacarbazine can be decreased when it is combined with Sorafenib.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Dacarbazine.
TeriflunomideThe serum concentration of Dacarbazine can be decreased when it is combined with Teriflunomide.
TofacitinibDacarbazine may increase the immunosuppressive activities of Tofacitinib.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Dacarbazine.
TrastuzumabTrastuzumab may increase the neutropenic activities of Dacarbazine.
VemurafenibThe serum concentration of Dacarbazine can be increased when it is combined with Vemurafenib.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
cross-linking/alkylation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Lonn U, Lohn S: Prevention of dacarbazine damage of human neoplastic cell DNA by aphidicolin. Cancer Res. 1987 Jan 1;47(1):26-30. [PubMed:3098406 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
General Function:
Protein heterodimerization activity
Specific Function:
May play an essential role at the early stage of chromosomal DNA replication by coupling the polymerase alpha/primase complex to the cellular replication machinery.
Gene Name:
POLA2
Uniprot ID:
Q14181
Molecular Weight:
65947.165 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. Lonn U, Lohn S: Prevention of dacarbazine damage of human neoplastic cell DNA by aphidicolin. Cancer Res. 1987 Jan 1;47(1):26-30. [PubMed:3098406 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Phosphogluconate dehydrogenase (decarboxylating) activity
Specific Function:
Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
Gene Name:
PGD
Uniprot ID:
P52209
Molecular Weight:
53139.56 Da
References
  1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Aug;25(4):476-9. doi: 10.3109/14756360903257900. [PubMed:20235752 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d 24-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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 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 ]
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Drug created on June 13, 2005 07:24 / Updated on October 22, 2013 22:29