U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C6H10N6O
Molecular Weight 182.1834
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DACARBAZINE

SMILES

CN(C)/N=N/c1c(C(=O)N)nc[nH]1

InChI

InChIKey=FDKXTQMXEQVLRF-ZHACJKMWSA-N
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+

HIDE SMILES / InChI
Molecular Formula C6H10N6O
Molecular Weight 182.1834
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

Dacarbazine (DTIC), also known as imidazole carboxamide, is an antineoplastic agent, which is used in the treatment of metastatic malignant melanoma. In addition, this drug also is indicated for Hodgkin’s disease as a second-line therapy when used in combination with other effective agents. Dacarbazine works by methylating guanine at the O-6 and N-7 positions. Guanine is one of the four nucleotides that makes up DNA. The alkylated DNA strands stick together such that cell division becomes impossible. This affects cancer cells more than healthy cells because cancer cells divide faster. Dacarbazine is bioactivated in liver by demethylation to "MTIC" and then to diazomethane, which is an alkylating agent. Symptoms of anorexia, nausea, and vomiting are the most frequently noted of all toxic reactions. Over 90% of patients are affected with the initial few doses.

CNS Activity

Originator

Approval Year

1975
48
Targets

Targets

Primary TargetPharmacologyConditionPotency
DNA
232
Target ID: CHEMBL2311221
Inhibitor
7728
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8043
DTIC-DOME

Approved Use

Dacarbazine for Injection USP is indicated in the treatment of metastatic malignant melanoma. In addition, Dacarbazine for Injection USP is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other effective agents.

Launch Date

1.70380804E11
Primary
Approved
8043
DTIC-DOME

Approved Use

Dacarbazine for Injection USP is indicated in the treatment of metastatic malignant melanoma. In addition, Dacarbazine for Injection USP is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other effective agents.

Launch Date

1.70380804E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
6.2 μg/mL
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/26940170
750 mg/m² single, intravenous
dose: 750 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DACARBAZINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
14.8 μM × min
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/26940170
750 mg/m² single, intravenous
dose: 750 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DACARBAZINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
41.4 min
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/26940170
750 mg/m² single, intravenous
dose: 750 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DACARBAZINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
95%
OTHER GOV
https://www.medicines.org.uk/emc/product/7747/smpc
DACARBAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1000 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 1000 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1000 mg/m2, 1 times / 3 weeks
Co-administed with::
Lenalidomide, p.o(5 mg/day; 14 days)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503, 504
unhealthy, 34–79
n = 3
Health Status: unhealthy
Condition: Malignant melanoma
Age Group: 34–79
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503, 504
Disc. AE: Cerebral ischemia...
AEs leading to
discontinuation/dose reduction:
Cerebral ischemia (grade 4, 33%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503, 504
800 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 800 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 800 mg/m2, 1 times / 3 weeks
Co-administed with::
Lenalidomide, p.o(5 mg/day; 14 days)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503
unhealthy, 34–79
n = 16
Health Status: unhealthy
Condition: Malignant melanoma
Age Group: 34–79
Sex: M+F
Population Size: 16
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503
DLT: Thrombocytopenia...
Disc. AE: Thrombocytopenia...
Dose limiting toxicities:
Thrombocytopenia (grade 2, 6.25%)
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (grade 1, 6.25%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503
1000 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 1000 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1000 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/23735514
Page: p.5
unhealthy, 40–65
n = 45
Health Status: unhealthy
Condition: Malignant melanoma
Age Group: 40–65
Sex: M+F
Population Size: 45
Sources:
https://pubmed.ncbi.nlm.nih.gov/23735514
Page: p.5
Other AEs: Neutropenia, Fatigue...
Other AEs:
Neutropenia (grade 4, 2.2%)
Fatigue (grade 4, 2.2%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/23735514
Page: p.5
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Disc. AE: Leukopenia, Thrombocytopenia...
AEs leading to
discontinuation/dose reduction:
Leukopenia (grade 3-5)
Thrombocytopenia (grade 3-5)
Anemia (sometimes)
Hematopoiesis impaired
Hepatotoxicity (grade 3-5, 0.01%)
Hepatic vein thrombosis (grade 3-5, 0.01%)
Necrosis hepatocellular (grade 3-5, 0.01%)
Anaphylaxis
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 850 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 850 mg/m2, 1 times / 3 weeks
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
Disc. AE: Anemia, Leukopenia...
AEs leading to
discontinuation/dose reduction:
Anemia (mild)
Leukopenia (grade 3-5)
Thrombocytopenia (grade 3-5)
Hepatotoxicity (grade 3-5)
Hepatic vein thrombosis (grade 3-5)
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
AEs

AEs

AESignificanceDosePopulation
Cerebral ischemia grade 4, 33%
Disc. AE
1000 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 1000 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1000 mg/m2, 1 times / 3 weeks
Co-administed with::
Lenalidomide, p.o(5 mg/day; 14 days)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503, 504
unhealthy, 34–79
n = 3
Health Status: unhealthy
Condition: Malignant melanoma
Age Group: 34–79
Sex: M+F
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503, 504
Thrombocytopenia grade 1, 6.25%
Disc. AE
800 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 800 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 800 mg/m2, 1 times / 3 weeks
Co-administed with::
Lenalidomide, p.o(5 mg/day; 14 days)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503
unhealthy, 34–79
n = 16
Health Status: unhealthy
Condition: Malignant melanoma
Age Group: 34–79
Sex: M+F
Population Size: 16
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503
Thrombocytopenia grade 2, 6.25%
DLT
800 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 800 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 800 mg/m2, 1 times / 3 weeks
Co-administed with::
Lenalidomide, p.o(5 mg/day; 14 days)
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503
unhealthy, 34–79
n = 16
Health Status: unhealthy
Condition: Malignant melanoma
Age Group: 34–79
Sex: M+F
Population Size: 16
Sources:
https://pubmed.ncbi.nlm.nih.gov/20859231
Page: p.503
Fatigue grade 4, 2.2%
1000 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 1000 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1000 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/23735514
Page: p.5
unhealthy, 40–65
n = 45
Health Status: unhealthy
Condition: Malignant melanoma
Age Group: 40–65
Sex: M+F
Population Size: 45
Sources:
https://pubmed.ncbi.nlm.nih.gov/23735514
Page: p.5
Neutropenia grade 4, 2.2%
1000 mg/m2 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 1000 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 1000 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/23735514
Page: p.5
unhealthy, 40–65
n = 45
Health Status: unhealthy
Condition: Malignant melanoma
Age Group: 40–65
Sex: M+F
Population Size: 45
Sources:
https://pubmed.ncbi.nlm.nih.gov/23735514
Page: p.5
Anaphylaxis Disc. AE
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Hematopoiesis impaired Disc. AE
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Hepatic vein thrombosis grade 3-5, 0.01%
Disc. AE
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Hepatotoxicity grade 3-5, 0.01%
Disc. AE
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Necrosis hepatocellular grade 3-5, 0.01%
Disc. AE
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Leukopenia grade 3-5
Disc. AE
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Thrombocytopenia grade 3-5
Disc. AE
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Anemia sometimes
Disc. AE
250 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 250 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 250 mg/m2, 1 times / day
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b6b97e41-5f15-498c-abfb-d8443ea4d216&type=display
Hepatic vein thrombosis grade 3-5
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 850 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 850 mg/m2, 1 times / 3 weeks
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
Hepatotoxicity grade 3-5
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 850 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 850 mg/m2, 1 times / 3 weeks
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
Leukopenia grade 3-5
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 850 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 850 mg/m2, 1 times / 3 weeks
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
Thrombocytopenia grade 3-5
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 850 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 850 mg/m2, 1 times / 3 weeks
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
Anemia mild
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
Dose: 850 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 850 mg/m2, 1 times / 3 weeks
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
unhealthy
Health Status: unhealthy
Condition: Malignant melanoma
Sources:
https://www.ema.europa.eu/en/documents/referral/summary-information-referral-opinion-following-arbitration-pursuant-article-29-directive-2001/83/ec-formerly-article-10-paragraph-2-directive-75/319/eec-20-may-1975-amended-dacarbazine-fauld_en.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1601
substrate
936

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2C19
1325
CYP1A2
972

CYP1A1
325

CYP2E1
606
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
1392
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C9
936
 no
CYP3A4
1601
 no
CYP1A1
325
 yes
CYP1A2
972
 yes
CYP2E1
606
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:4305
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4305
MolPort
MolPort-044-723-991
https://www.molport.com/shop/molecule-link/MolPort-044-723-991
ZINC
ZINC000254748682
http://zinc15.docking.org/substances/ZINC000254748682
eMolecules
37036088
https://www.emolecules.com/cgi-bin/more?vid=37036088
PubMed

PubMed

TitleDatePubMed
Cardiomyopathy after widely separated courses of adriamycin exacerbated by actinomycin-D and mithramycin.
1975 Nov
[DTIC: effect on fibrinolysis and thrombocyte function].
1986 Oct
Peripheral DTIC neurotoxicity: a case report.
1987
Fatal hepatic vascular toxicity of DTIC. Is it really a rare event?
1988 May 15
Hepatic vascular toxicity of dacarbazine (DTIC): not a rare complication.
1989 May
[Hepatic veno-occlusive disease caused by Deticene: a cause of acute hypovolemic shock].
1990
Dana-Farber Cancer Institute studies in advanced sarcoma.
1990 Feb
Successful palliation of stenosing anorectal melanoma by intratumoral injections with natural interferon-beta.
2002 Aug
Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene elicits a specific T cell-dependent immune response.
2002 Oct
Effect of a novel somatostatin analogue combined with cytotoxic drugs on human tumour xenografts and metastasis of B16 melanoma.
2003 Jan 13
Second-line chemotherapy with dacarbazine and fotemustine in nitrosourea-pretreated patients with recurrent glioblastoma multiforme.
2003 Jul
Metastatic melanoma presenting as cardiac mass and hemobilia.
2003 Mar
O6-methylguanine-DNA-methyltransferase expression and gene polymorphisms in relation to chemotherapeutic response in metastatic melanoma.
2003 Oct 20
A humanized monoclonal antibody to carcinoembryonic antigen, labetuzumab, inhibits tumor growth and sensitizes human medullary thyroid cancer xenografts to dacarbazine chemotherapy.
2004 Dec
Serum bcl-2 and survivin levels in melanoma.
2004 Dec
Activity of irinotecan, cisplatin and dacarbazine (CPD) combination in previously treated patients with advanced colorectal carcinoma.
2004 Jun
Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo.
2004 Jun 1
Correspondence re: DC Lev et al., Dacarbazine causes transcriptional up-regulation of interleukin 8 and vascular endothelial growth factor in melanoma cells: a possible escape mechanism from chemotherapy. Mol Cancer Ther, 2003;2(8):753-63.
2004 Mar
Thalidomide enhances the anti-tumor activity of standard chemotherapy in a human melanoma xenotransplatation model.
2005 Aug
Randomized trial of dacarbazine versus bleomycin, vincristine, lomustine and dacarbazine (BOLD) chemotherapy combined with natural or recombinant interferon-alpha in patients with advanced melanoma.
2005 Aug
Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281.
2005 Aug 1
Functional erythropoietin autocrine loop in melanoma.
2005 Mar
A retrospective study of biochemotherapy for metastatic melanoma: the importance of dose intensity.
2005 Oct
Long-term survival benefit after adjuvant treatment of cutaneous melanoma with dacarbazine and low dose natural interferon alpha: A controlled, randomised multicentre trial.
2006
Long-term survival in metastatic melanoma patients treated with sequential biochemotherapy: report of a Phase II study.
2006 Aug-Sep
Chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha2b and interleukin-2 versus two cycles of dacarbazine followed by chemoimmunotherapy in patients with metastatic melanoma: a randomised phase II study of the European Organization for Research and Treatment of Cancer Melanoma Group.
2006 Nov
Intralesional therapy of metastatic spreading melanoma with beta-interferon.
2006 Sep
Single-agent interleukin-2 in the treatment of metastatic melanoma.
2007 Feb
Resection in the popliteal fossa for metastatic melanoma.
2007 Jan 19
Hemorrhagic cystitis in a patient receiving conventional doses of dacarbazine for metastatic malignant melanoma: case report and review of the literature.
2007 Jun
Combined treatment with Ad-hTRAIL and DTIC or SAHA is associated with increased mitochondrial-mediated apoptosis in human melanoma cell lines.
2007 Jun
CD69 on CD56+ NK cells and response to chemoimmunotherapy in metastatic melanoma.
2007 Nov
Adjuvant chemotherapy with doxorubicin and dacarbazine has no effect in recurrence-free survival of malignant phyllodes tumors of the breast.
2007 Nov-Dec
Results of a multicenter randomized study to evaluate the safety and efficacy of combined immunotherapy with interleukin-2, interferon-{alpha}2b and histamine dihydrochloride versus dacarbazine in patients with stage IV melanoma.
2007 Oct
Durable complete responses with high-dose bolus interleukin-2 in patients with metastatic melanoma who have experienced progression after biochemotherapy.
2007 Sep 1
Biochemotherapy of metastatic melanoma in patients with or without recently diagnosed brain metastases.
2007 Sep 15
The management of desmoids in patients with familial adenomatous polyposis (FAP).
2008
Influence of therapy on the antioxidant status in patients with melanoma.
2008 Apr
The "old drug" dacarbazine as a second/third line chemotherapy in advanced soft tissue sarcomas.
2008 Apr
Multicenter phase II study of chemoimmunotherapy in the treatment of metastatic melanoma.
2008 Feb
Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group.
2008 Feb 20
Meta-analysis of ifosfamide-based combination chemotherapy in advanced soft tissue sarcoma.
2008 Jun
Cerebellar dysfunction caused by procarbazine and consumption of excessive amount of bananas.
2008 Jun
Plitidepsin has a dual effect inhibiting cell cycle and inducing apoptosis via Rac1/c-Jun NH2-terminal kinase activation in human melanoma cells.
2008 Mar
Glut-1 as a therapeutic target: increased chemoresistance and HIF-1-independent link with cell turnover is revealed through COMPARE analysis and metabolomic studies.
2008 Mar
Unexpected clinical outcome in a patient with liver and brain metastasis from melanoma.
2008 Mar-Apr
Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group.
2008 May 1
Impairment of APE1 function enhances cellular sensitivity to clinically relevant alkylators and antimetabolites.
2009 Jun
Glucocorticoid-dependent expression of O(6)-methylguanine-DNA methyltransferase gene modulates dacarbazine-induced hepatotoxicity in mice.
2010 Jun
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.
2014 Jan
Patents

Patents

US2004063677
3
US6573284
3
US6653331
3

Sample Use Guides

In Vivo Use Guide
Malignant Melanoma: the recommended dosage is 2 to 4.5 mg/kg/day for 10 days. Treatment may be repeated at 4 week intervals Hodgkin's Disease: The recommended dosage of Dacarbazine for Injection, USP in the treatment of Hodgkin’s disease is 150 mg/square meter body surface/day for 5 days, in combination with other effective drugs. Treatment may be repeated every 4 weeks.5 An alternative recommended dosage is 375 mg/square meter body surface on day 1, in combination with other effective drugs, to be repeated every 15 days
Route of Administration: Intravenous
In Vitro Use Guide
The effect of alkyating agent dacarbazine (DTIC) and imexon, alone and in combination, was evaluated for growth inhibition (MTT), radiolabeled drug uptake, cellular thiol content (HPLC), and DNA strand breaks (Comet assay). Growth inhibition in vitro was additive with the two drugs. There was no effect on drug uptake or on the number of DNA strand breaks. There was a >75% reduction in cellular glutathione and cysteine with imexon but not DTIC. Co-administration of the two drugs in mice caused an increase in the area under the curve of both drugs, but the combination was not effective in reducing human A375 melanoma tumors in vivo.
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:53:40 UTC 2021
Edited
by admin
on Fri Jun 25 20:53:40 UTC 2021
Record UNII
7GR28W0FJI
Record Status Validated (UNII)
Record Version
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Name Type Language
DACARBAZINE
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
USAN   INN  
Official Name English
DACARBAZINE [WHO-IP]
Common Name English
DIC
Common Name English
DTIC
Common Name English
DACARBAZINE [WHO-DD]
Common Name English
DACARBASINE
Common Name English
DACARBAZINE [INN]
Common Name English
1H-IMIDAZOLE-4-CARBOXAMIDE, 5-(3,3-DIMETHYL-1-TRIAZENYL)-
Systematic Name English
DACARBAZINE [ORANGE BOOK]
Common Name English
DACARBAZINE [USP MONOGRAPH]
Common Name English
DACARBAZINE [HSDB]
Common Name English
DTIC-DOME
Brand Name English
DACARBAZINE [USP-RS]
Common Name English
DACARBAZINE [MI]
Common Name English
DACARBAZINE [VANDF]
Common Name English
NSC-45388
Code English
NCI C04717
Code English
DACARBAZINE [IARC]
Common Name English
DACARBAZINE [EP MONOGRAPH]
Common Name English
IMIDAZOLE CARBOXAMIDE
Systematic Name English
DACARBAZINE [USAN]
Common Name English
DACARBAZINE [MART.]
Common Name English
DACARBAZINUM [WHO-IP LATIN]
Common Name English
DACARBAZINE [JAN]
Common Name English
5-(3,3-DIMETHYL-1-TRIAZENO)IMIDAZOLE-4-CARBOXAMIDE
Systematic Name English
BIOCARBAZINE R
Common Name English
DICARBAZINE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C902
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
LIVERTOX 256
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
WHO-ATC L01AX04
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
NDF-RT N0000175558
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
WHO-VATC QL01AX04
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 8.2
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
Code System Code Type Description
INN
3232
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
FDA UNII
7GR28W0FJI
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
DRUG BANK
DB00851
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
LACTMED
Dacarbazine
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
WIKIPEDIA
DACARBAZINE
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
USP_CATALOG
1162308
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY USP-RS
HSDB
3219
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
CAS
4342-03-4
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
NCI_THESAURUS
C411
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
EPA CompTox
4342-03-4
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
PUBCHEM
135398738
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
ECHA (EC/EINECS)
224-396-1
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
ChEMBL
CHEMBL476
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
DACARBAZINE
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY Description: A colourless or pale yellow, crystalline powder.Solubility: Slightly soluble in water and ethanol (~750 g/l) TS.Category: Cytotoxic drug.Storage: Dacarbazine should be kept in a tightly closed container, protected from light, and stored at a temperature notexceeding 8 ?C.Additional information: CAUTION: Dacarbazine must be handled with care, avoiding contact with the skin and inhalation ofairborne particles.
MERCK INDEX
M4065
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY Merck Index
EVMPD
SUB06882MIG
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
MESH
D003606
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
DRUG CENTRAL
773
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY
RXCUI
3098
Created by admin on Fri Jun 25 20:53:40 UTC 2021 , Edited by admin on Fri Jun 25 20:53:40 UTC 2021
PRIMARY RxNorm
Related Record Type Details
CYTOCHROME P450 2E1
METABOLIC ENZYME -> SUBSTRATE
Km
CYTOCHROME P450 1A1
METABOLIC ENZYME -> SUBSTRATE
Vmax
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
Vmax
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Structure of DACARBAZINE CITRATE
SALT/SOLVATE -> PARENT
Structure of DACARBAZINE HYDROCHLORIDE
SALT/SOLVATE -> PARENT
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
Km
CYTOCHROME P450 1A1
METABOLIC ENZYME -> SUBSTRATE
Km
Related Record Type Details
Structure of 4-AMINO-5-IMIDAZOLE CARBOXAMIDE
METABOLITE INACTIVE -> PARENT
Plasma exposure to AIC was equivalent to that of DTIC, whereas urinary recovery of DTIC and AIC was low and highly variable.
MAJOR
PLASMA
Structure of FORMALDEHYDE
METABOLITE -> PARENT
Structure of HMMTIC
METABOLITE ACTIVE -> PRODRUG
Structure of 2-AZAHYPOXANTHINE
METABOLITE -> PARENT
Structure of N-NITROSOMETHYLAMINE
METABOLITE ACTIVE -> PRODRUG
Structure of HMMTIC
METABOLITE -> PARENT
Structure of MTIC
METABOLITE ACTIVE -> PRODRUG
PLASMA
Related Record Type Details
Structure of 2-AZAHYPOXANTHINE
IMPURITY -> PARENT
Structure of 4-AMINO-5-IMIDAZOLE CARBOXAMIDE
IMPURITY -> PARENT
Structure of DIMETHYLAMINE
IMPURITY -> PARENT
Structure of 5-DIAZENYL-1H-IMIDAZOLE-4-CARBOXAMIDE
IMPURITY -> PARENT
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
NIH
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