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Details

Stereochemistry ACHIRAL
Molecular Formula C6H10N6O.ClH
Molecular Weight 218.644
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DACARBAZINE HYDROCHLORIDE

SMILES

Cl.CN(C)\N=N\C1=C(N=CN1)C(N)=O

InChI

InChIKey=JTLLDOORGJVYPT-ASTDGNLGSA-N
InChI=1S/C6H10N6O.ClH/c1-12(2)11-10-6-4(5(7)13)8-3-9-6;/h3H,1-2H3,(H2,7,13)(H,8,9);1H/b11-10+;

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C6H10N6O
Molecular Weight 182.1832
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2311221
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
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
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
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
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%
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: 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: Page: p.503, 504
Disc. AE: Cerebral ischemia...
AEs leading to
discontinuation/dose reduction:
Cerebral ischemia (grade 4, 33%)
Sources: 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: 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: 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: 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: 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: Page: p.5
Other AEs: Neutropenia, Fatigue...
Other AEs:
Neutropenia (grade 4, 2.2%)
Fatigue (grade 4, 2.2%)
Sources: 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:
unhealthy
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:
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
unhealthy
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:
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
Hepatic vein thrombosis grade 3-5
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
unhealthy
Hepatotoxicity grade 3-5
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
unhealthy
Leukopenia grade 3-5
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
unhealthy
Thrombocytopenia grade 3-5
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
unhealthy
Anemia mild
Disc. AE
850 mg/m2 1 times / 3 weeks multiple, intravenous
Recommended
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
Drug as victim
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
Thalidomide enhances the anti-tumor activity of standard chemotherapy in a human melanoma xenotransplatation model.
2005 Aug
Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) in human melanoma and identification of the therapeutic potential of resveratrol as an APE/Ref-1 inhibitor.
2005 Dec
Artesunate in the treatment of metastatic uveal melanoma--first experiences.
2005 Dec
Organ- and treatment-specific local response rates to systemic and local treatment modalities in stage IV melanoma.
2005 Nov
A retrospective study of biochemotherapy for metastatic melanoma: the importance of dose intensity.
2005 Oct
Sarcomatoid renal cell carcinoma with a chromophobe component producing beta-human chorionic gonadotropin.
2005 Sep
Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group.
2005 Sep 20
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
Alkylating benzamides with melanoma cytotoxicity: experimental chemotherapy in a mouse melanoma model.
2006 Dec
[Hypersensitivity to dacarbazine in patients with metastatic malignant melanoma].
2006 Feb
Phase II multicenter study of neoadjuvant biochemotherapy for patients with stage III malignant melanoma.
2006 Jul 1
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
Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group.
2006 Oct 10
Intralesional therapy of metastatic spreading melanoma with beta-interferon.
2006 Sep
Interleukin-2-based biochemotherapy for patients with stage IV melanoma: long-term survivors outside a clinical trial setting.
2007
Serum VEGF-C is associated with metastatic site in patients with malignant melanoma.
2007
Single-agent interleukin-2 in the treatment of metastatic melanoma.
2007 Feb
Resection in the popliteal fossa for metastatic melanoma.
2007 Jan 19
Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group.
2007 Jul
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
Comparison of a treatment strategy combining CCI-779 plus DTIC versus DTIC monotreatment in human melanoma in SCID mice.
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
Hodgkin lymphoma presenting with various immunologic abnormalities, including autoimmune hepatitis, Hashimoto's thyroiditis, autoimmune hemolytic anemia, and immune thrombocytopenia.
2008 Feb
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

Sample Use Guides

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
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 Sat Dec 16 08:18:27 UTC 2023
Edited
by admin
on Sat Dec 16 08:18:27 UTC 2023
Record UNII
IBG90R0OVS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DACARBAZINE HYDROCHLORIDE
Common Name English
5-(3,3-DIMETHYL-1-TRIAZENO)IMIDAZOLE-4-CARBOXAMIDE HYDROCHLORIDE
Systematic Name English
1H-IMIDAZOLE-4-CARBOXAMIDE, 5-(3,3-DIMETHYL-1-TRIAZEN-1-YL)-, HYDROCHLORIDE (1:1)
Systematic Name English
Code System Code Type Description
FDA UNII
IBG90R0OVS
Created by admin on Sat Dec 16 08:18:27 UTC 2023 , Edited by admin on Sat Dec 16 08:18:27 UTC 2023
PRIMARY
CAS
17925-90-5
Created by admin on Sat Dec 16 08:18:27 UTC 2023 , Edited by admin on Sat Dec 16 08:18:27 UTC 2023
PRIMARY
PUBCHEM
135565185
Created by admin on Sat Dec 16 08:18:27 UTC 2023 , Edited by admin on Sat Dec 16 08:18:27 UTC 2023
PRIMARY
CAS
21299-67-2
Created by admin on Sat Dec 16 08:18:27 UTC 2023 , Edited by admin on Sat Dec 16 08:18:27 UTC 2023
NON-SPECIFIC STOICHIOMETRY
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