Identification

Name
Dacarbazine
Accession Number
DB00851  (APRD00331)
Type
Small Molecule
Groups
Approved, 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
  • DTIC
  • ICDMT
External IDs
HSDB 3219 / NCI C04717 / NCI-C04717 / NSC 45 388 / NSC 45388 / NSC-45388
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dacarbazine for Injection BPPowder, for solution600 mgIntravenousPfizer2000-04-04Not applicableCanada
Dtic Dome Inj 200mg/vialLiquid200 mgIntravenousMiles Inc. Pharmaceutical Division1976-12-311998-09-25Canada
Dtic-dome -pws IV 200mg/vialPowder, for solution10 mgIntravenousBayer1996-10-102005-05-31Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DacarbazineInjection, powder, for solution10 mg/1mLIntravenousFresenius Kabi USA, LLC2001-09-07Not applicableUs
DacarbazineInjection, powder, lyophilized, for solution10 mg/1mLIntravenousBedford Pharmaceuticals2001-08-082013-05-31Us
DacarbazineInjection, powder, for solution10 mg/1mLIntravenousHospira, Inc.2003-07-01Not applicableUs
DacarbazineInjection, powder, for solution200 mg/20mLIntravenousTeva Parenteral Medicines, Inc.1998-08-27Not applicableUs
DacarbazineInjection, powder, for solution10 mg/1mLIntravenousFresenius Kabi USA, LLC2001-09-07Not applicableUs
DacarbazineInjection, powder, lyophilized, for solution200 mg/20mLIntravenousBedford Pharmaceuticals2008-03-032012-12-31Us
International/Other Brands
Dacatic (Orion Corporation) / Déticène (Sanofi-Aventis) / Deticene (Sanofi-Aventis) / Detimedac (medac GmbH) / DTIC (Bayer AG) / DTIC-Dome (Bayer Schering)
Categories
UNII
7GR28W0FJI
CAS number
4342-03-4
Weight
Average: 182.187
Monoisotopic: 182.091608966
Chemical Formula
C6H10N6O
InChI Key
FDKXTQMXEQVLRF-ZHACJKMWSA-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)/b11-10+
IUPAC Name
5-[(1E)-3,3-dimethyltriaz-1-en-1-yl]-1H-imidazole-4-carboxamide
SMILES
CN(C)\N=N\C1=C(N=CN1)C(N)=O

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Dacarbazine 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 action

The 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.

TargetActionsOrganism
ADNA
cross-linking/alkylation
Human
UDNA polymerase alpha subunit B
other/unknown
Human
U6-phosphogluconate dehydrogenase, decarboxylating
inhibitor
Human
Absorption

Erratic, slow and incomplete.

Volume of distribution
Not Available
Protein binding

Less than 5%

Metabolism

Hepatic

Route of elimination

Dacarbazine 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 life

5 hours

Clearance
Not Available
Toxicity

LD50=350mg/kg (orally in mice)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Dacarbazine.
(S)-WarfarinThe risk or severity of bleeding can be increased when (S)-Warfarin is combined with Dacarbazine.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Dacarbazine is combined with 2-Methoxyethanol.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Dacarbazine.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Dacarbazine.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be increased when it is combined with Dacarbazine.
7-DeazaguanineThe serum concentration of 7-Deazaguanine can be increased when it is combined with Dacarbazine.
7,9-DimethylguanineThe serum concentration of 7,9-Dimethylguanine can be increased when it is combined with Dacarbazine.
8-azaguanineThe serum concentration of 8-azaguanine can be increased when it is combined with Dacarbazine.
8-chlorotheophyllineThe serum concentration of 8-chlorotheophylline can be increased when it is combined with Dacarbazine.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D00288
KEGG Compound
C06936
PubChem Compound
5351166
PubChem Substance
46507029
ChemSpider
10481959
ChEBI
4305
ChEMBL
CHEMBL476
Therapeutic Targets Database
DAP000533
PharmGKB
PA449197
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dacarbazine
ATC Codes
L01AX04 — Dacarbazine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentCancer, Breast / Colon Neoplasms / Lung Cancers / Malignant Neoplasm of Colon / Melanoma / Neoplasms, Breast / Renal Cancers1
1CompletedTreatmentAdvanced Melanoma1
1CompletedTreatmentCarcinoid Tumors / Lung Cancer Small Cell Lung Cancer (SCLC) / Melanoma / Parathyroid Carcinoma / Soft Tissue Sarcoma (STS)1
1CompletedTreatmentHodgkins Disease (HD)1
1CompletedTreatmentLymphoma, Hodgkins1
1CompletedTreatmentMelanoma1
1CompletedTreatmentMelanoma Neoplasms1
1CompletedTreatmentStage IV Melanoma1
1, 2Active Not RecruitingTreatmentMetastatic Melanoma Stage IV1
1, 2CompletedTreatmentMalignant Melanoma2
1, 2CompletedTreatmentMelanoma1
1, 2CompletedTreatmentMetastatic Melanoma1
1, 2CompletedTreatmentSarcomas1
1, 2CompletedTreatmentStage IV Melanoma1
1, 2RecruitingTreatmentAIDS-Related Hodgkin Lymphoma / Ann Arbor Stage II Hodgkin Lymphoma / Ann Arbor Stage IIA Hodgkin Lymphoma / Ann Arbor Stage IIB Hodgkin Lymphoma / Ann Arbor Stage III Hodgkin Lymphoma / Ann Arbor Stage IIIA Hodgkin Lymphoma / Ann Arbor Stage IIIB Hodgkin Lymphoma / Ann Arbor Stage IV Hodgkin Lymphoma / Ann Arbor Stage IVA Hodgkin Lymphoma / Ann Arbor Stage IVB Hodgkin Lymphoma / CD30-Positive Neoplastic Cells Present / Classic Hodgkin Lymphoma / Classical Hodgkin Lymphoma / Human Immunodeficiency Virus (HIV) Infections / Stage II Hodgkin Lymphoma / Stage IIA Hodgkin Lymphoma / Stage IIB Hodgkin Lymphoma / Stage III Hodgkin Lymphoma / Stage IIIA Hodgkin Lymphoma / Stage IIIB Hodgkin Lymphoma / Stage IV Hodgkin Lymphoma / Stage IVA Hodgkin Lymphoma / Stage IVB Hodgkin Lymphoma1
1, 2RecruitingTreatmentHodgkins Disease (HD)1
1, 2RecruitingTreatmentLymphoma, Hodgkins1
1, 2SuspendedTreatmentMelanoma1
1, 2TerminatedTreatmentMelanoma1
1, 2TerminatedTreatmentThyroid Cancers / Tumors, Solid1
2Active Not RecruitingTreatmentAdult Lymphocyte Depletion Hodgkin Lymphoma / Adult Lymphocyte Predominant Hodgkin Lymphoma / Adult Mixed Cellularity Hodgkin Lymphoma / Adult Nodular Sclerosis Hodgkin Lymphoma / Stage II Adult Hodgkin Lymphoma / Stage III Adult Hodgkin Lymphoma / Stage IV Adult Hodgkin Lymphoma1
2Active Not RecruitingTreatmentCiliary Body and Choroid Melanoma, Medium/Large Size / Ciliary Body and Choroid Melanoma, Small Size / Iris Melanoma / Recurrent Intraocular Melanoma1
2Active Not RecruitingTreatmentHIV-associated Hodgkin Lymphoma / Human Immunodeficiency Virus (HIV) Infections / Stage III Adult Hodgkin Lymphoma / Stage IV Adult Hodgkin Lymphoma1
2Active Not RecruitingTreatmentHodgkins Disease (HD)1
2Active Not RecruitingTreatmentIris Melanoma / Medium/Large Size Posterior Uveal Melanoma / Ocular Melanoma With Extraocular Extension / Recurrent Uveal Melanoma / Small Size Posterior Uveal Melanoma / Stage IV Uveal Melanoma1
2Active Not RecruitingTreatmentLymphoma, Hodgkins1
2Active Not RecruitingTreatmentMalignant Lymphomas / Nonneoplastic Condition1
2Active Not RecruitingTreatmentMalignant Melanoma1
2Active Not RecruitingTreatmentMetastatic Melanoma1
2Active Not RecruitingTreatmentMetastatic Uveal Melanoma1
2Active Not RecruitingTreatmentStage II Childhood Hodgkin Lymphoma / Stage III Childhood Hodgkin Lymphoma / Stage IV Childhood Hodgkin Lymphoma1
2CompletedPreventionMelanoma1
2CompletedTreatmentCarcinoma, Melanoma1
2CompletedTreatmentHodgkins Disease (HD) / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentLeiomyosarcomas / Malignant Peripheral Nerve Sheath Tumour (MPNST) / Sarcomas / Synovial Sarcoma1
2CompletedTreatmentLymphoma, Hodgkins3
2CompletedTreatmentMalignancies / Melanoma1
2CompletedTreatmentMalignant Lymphomas6
2CompletedTreatmentMalignant Melanoma2
2CompletedTreatmentMalignant Metastatic Melanoma / Melanoma1
2CompletedTreatmentMelanoma5
2CompletedTreatmentMelanoma (Skin)2
2CompletedTreatmentMetastatic Malignant Melanoma1
2CompletedTreatmentMetastatic Melanoma1
2CompletedTreatmentN-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous Melanoma1
2CompletedTreatmentNeuroblastomas1
2CompletedTreatmentRecurrent Uveal Melanoma / Stage III Uveal Melanoma / Stage III Uveal Melanoma AJCC v7 / Stage IIIA Uveal Melanoma / Stage IIIA Uveal Melanoma AJCC v7 / Stage IIIB Uveal Melanoma / Stage IIIB Uveal Melanoma AJCC v7 / Stage IIIC Uveal Melanoma / Stage IIIC Uveal Melanoma AJCC v7 / Stage IV Uveal Melanoma / Stage IV Uveal Melanoma AJCC v71
2CompletedTreatmentSarcomas2
2CompletedTreatmentStage III Melanoma / Stage IV Melanoma1
2Not Yet RecruitingTreatmentAdvanced Hodgkin's Lymphoma1
2Not Yet RecruitingTreatmentClassical Hodgkin Lymphoma1
2RecruitingTreatmentAnn Arbor Stage I Hodgkin Lymphoma / Ann Arbor Stage I Lymphocyte-Depleted Classic Hodgkin Lymphoma / Ann Arbor Stage I Mixed Cellularity Classic Hodgkin Lymphoma / Ann Arbor Stage I Nodular Sclerosis Classic Hodgkin Lymphoma / Ann Arbor Stage IA Hodgkin Lymphoma / Ann Arbor Stage IB Hodgkin Lymphoma / Ann Arbor Stage II Hodgkin Lymphoma / Ann Arbor Stage II Lymphocyte-Depleted Classic Hodgkin Lymphoma / Ann Arbor Stage II Mixed Cellularity Classic Hodgkin Lymphoma / Ann Arbor Stage II Nodular Sclerosis Classic Hodgkin Lymphoma / Ann Arbor Stage IIA Hodgkin Lymphoma / Ann Arbor Stage IIB Hodgkin Lymphoma / Classic Hodgkin Lymphoma / Lymphocyte-Rich Classic Hodgkin Lymphoma1
2RecruitingTreatmentAnn Arbor Stage I Hodgkin Lymphoma / Ann Arbor Stage IA Hodgkin Lymphoma / Ann Arbor Stage IB Hodgkin Lymphoma / Ann Arbor Stage II Hodgkin Lymphoma / Ann Arbor Stage IIA Hodgkin Lymphoma / Ann Arbor Stage IIB Hodgkin Lymphoma / Stage I Hodgkin Lymphoma / Stage IA Hodgkin Lymphoma / Stage IB Hodgkin Lymphoma / Stage II Hodgkin Lymphoma / Stage IIA Hodgkin Lymphoma / Stage IIB Hodgkin Lymphoma1
2RecruitingTreatmentClassical Hodgkin Lymphoma1
2RecruitingTreatmentClassical Hodgkin Lymphoma / Hodgkin Lymphoma (Category) / Hodgkins Disease (HD) / Lymphoma, Hodgkins1
2RecruitingTreatmentClassical Hodgkin Lymphoma / Lymphocyte-Depleted Classical Hodgkin Lymphoma / Lymphocyte-Rich Classical Hodgkin Lymphoma / Mixed Cellularity Classical Hodgkin Lymphoma / Nodular Sclerosis Classical Hodgkin Lymphoma1
2RecruitingTreatmentHodgkins Disease (HD)1
2RecruitingTreatmentLymphoma, Hodgkins1
2RecruitingTreatmentMelanoma1
2RecruitingTreatmentNeuroendocrine Tumors1
2RecruitingTreatmentSolitary Fibrous Tumors1
2RecruitingTreatmentUveal Melanoma1
2TerminatedTreatmentClassic Hodgkin Lymphoma / Lugano Classification Stage III Hodgkin Lymphoma AJCC v8 / Lugano Classification Stage IV Hodgkin Lymphoma AJCC v8 / Lymphoma, Hodgkins1
2TerminatedTreatmentMalignant Lymphomas1
2TerminatedTreatmentMelanoma1
2TerminatedTreatmentMelanoma Metastatic1
2TerminatedTreatmentMetastatic Malignant Melanoma / Unresectable Malignant Melanoma1
2TerminatedTreatmentMetastatic Melanoma2
2TerminatedTreatmentRecurrent Adult Soft Tissue Sarcoma / Stage I Adult Soft Tissue Sarcoma / Stage I Adult Soft Tissue Sarcoma AJCC v7 / Stage II Adult Soft Tissue Sarcoma / Stage II Adult Soft Tissue Sarcoma AJCC v7 / Stage III Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma AJCC v71
2TerminatedTreatmentSarcomas1
2Unknown StatusTreatmentHIV-associated Hodgkin Lymphoma1
2Unknown StatusTreatmentHodgkins Disease (HD)1
2Unknown StatusTreatmentMalignant Lymphomas1
2Unknown StatusTreatmentMalignant Melanoma1
2Unknown StatusTreatmentMelanoma1
3Active Not RecruitingTreatmentLymphoma, Hodgkins4
3Active Not RecruitingTreatmentMalignant Lymphomas2
3Active Not RecruitingTreatmentMelanoma2
3Active Not RecruitingTreatmentMetastatic or Unresectable Cutaneous Melanoma1
3Active Not RecruitingTreatmentUnresectable or Metastatic Melanoma1
3CompletedTreatmentAdvanced Liposarcoma or Leiomyosarcoma1
3CompletedTreatmentAdvanced or Metastatic Liposarcoma or Leiomyosarcoma1
3CompletedTreatmentHodgkins Disease (HD)1
3CompletedTreatmentLymphoma, Hodgkins4
3CompletedTreatmentMalignancies1
3CompletedTreatmentMalignant Lymphomas3
3CompletedTreatmentMalignant Melanoma2
3CompletedTreatmentMalignant Melanoma / Recurrent Melanoma1
3CompletedTreatmentMelanoma3
3CompletedTreatmentMelanoma (Skin)4
3CompletedTreatmentMelanoma / Skin Cancers1
3CompletedTreatmentMetastatic Melanoma1
3CompletedTreatmentMetastatic / Uveal Melanoma1
3CompletedTreatmentNeuroblastomas1
3CompletedTreatmentRecurrent Melanoma / Stage III Melanoma / Stage IV Melanoma1
3RecruitingTreatmentAlveolar Soft Part Sarcoma (ASPS) / Leiomyosarcomas / Soft-Tissue Sarcoma / Synovial Sarcoma1
3RecruitingTreatmentClassical Hodgkin Lymphoma2
3RecruitingTreatmentLymphoma, Hodgkins1
3RecruitingTreatmentMetastatic Melanoma1
3TerminatedTreatmentMalignant Lymphomas2
3Unknown StatusTreatmentLymphoma, Hodgkins1
3Unknown StatusTreatmentMalignant Lymphomas1
3Unknown StatusTreatmentMelanoma1
3Unknown StatusTreatmentNeuroblastomas1
4RecruitingTreatmentAnkylosing Spondylitis (AS) / Spondyloarthritis, Axial1
4RecruitingTreatmentLymphoma, Hodgkins1
4Unknown StatusTreatmentMetastatic Melanoma1
Not AvailableRecruitingTreatmentClassical Hodgkins Lymphoma in Children and Adolescents1
Not AvailableRecruitingTreatmentLymphoma, Hodgkins1
Not AvailableRecruitingTreatmentNeuroblastomas1
Not AvailableUnknown StatusTreatmentMalignant Lymphomas1
Not AvailableUnknown StatusTreatmentMelanoma (Skin)1

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
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Hospira Inc.
  • Sicor Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous10 mg/1mL
Injection, powder, for solutionIntravenous200 mg/20mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, 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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)205 °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)6.64ChemAxon
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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 2-heteroaryl carboxamides. These are compounds containing a heteroaromatic ring that carries a carboxamide group.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Carboxylic acid derivatives
Direct Parent
2-heteroaryl carboxamides
Alternative Parents
Carbonylimidazoles / Vinylogous amides / Heteroaromatic compounds / Primary carboxylic acid amides / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
2-heteroaryl carboxamide / Imidazole-4-carbonyl group / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide / Primary carboxylic acid amide / Azacycle / Organoheterocyclic compound / Organic 1,3-dipolar compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not 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
Uniprot Name
DNA polymerase alpha subunit B
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
Uniprot Name
6-phosphogluconate dehydrogenase, decarboxylating
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 un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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]
  2. Reid JM, Kuffel MJ, Miller JK, Rios R, Ames MM: Metabolic activation of dacarbazine by human cytochromes P450: the role of CYP1A1, CYP1A2, and CYP2E1. Clin Cancer Res. 1999 Aug;5(8):2192-7. [PubMed:10473105]
  3. Kantrowitz-Gordon I, Hays K, Kayode O, Kumar AR, Kaplan HG, Reid JM, Safgren SL, Ames MM, Easterling TR, Hebert MF: Pharmacokinetics of dacarbazine (DTIC) in pregnancy. Cancer Chemother Pharmacol. 2018 Mar;81(3):455-460. doi: 10.1007/s00280-017-3511-6. Epub 2018 Jan 5. [PubMed:29305638]
  4. Dacarbazine monograph [File]
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 ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
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]

Drug created on June 13, 2005 07:24 / Updated on November 17, 2018 07:13