Dacarbazine

Names

[ Name ]:
Dacarbazine

[Synonym ]:
dtic-aome
1H-Imidazole-4-carboxamide, 5-[(1E)-3,3-dimethyl-1-triazen-1-yl]-
5-(3,3-Dimethyltriazeno)imidazole-4-carboxamide
Dtic-Dome
DTIC
DTIE
5-(3,3-Dimethyltriaz-1-en-1-yl)-1H-imidazole-4-carboxamide
5-(3,3-Dimethyl-1-triazenyl)imidazole-4-carboxamide,DTIC
EINECS 224-396-1
1H-imidazole-5-carboxamide, 4-[(1E)-3,3-dimethyl-1-triazenyl]-
5-[(1E)-3,3-Dimethyltriaz-1-en-1-yl]-1H-imidazole-4-carboxamide
Dacarbazine
5-(3,3-Dimethyl-1-triazenyl)imidazole-4-carboxamide DTIC
5-(3,3-dimethyl-l-triazenyl)imidazole-4-carboxamide
1H-Imidazole-4-carboxamide, 5- (3,3-dimethyl-1-triazenyl)-
MFCD00057167
5-(3,3-dimethyltriazen-1-yl)-imidazole-4-carboxamide
DTIC Dome
DICARBAZINE
5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide
5-(3,3-dimethyl-1-triazenyl)imidazole-4-carboxamide
deticene
4-[(1E)-3,3-Dimethyl-1-triazen-1-yl]-1H-imidazole-5-carboxamide
DIC

Biological Activity

[Description]:

Dacarbazine(DTIC-Dome; DTIC) is an antineoplastic agent. It has significant activity against melanomas.Target: Nucleoside antimetabolite/analogApproved: May 1975Dacarbazine (DTIC) is the only single-agent approved by the Food and Drug Administration for treating metastatic melanoma. With DTIC as single agent, an approximately 20% objective response rate can be achieved with median response duration of 5 to 6 months and complete response rates of 5% [1]. Dacarbazine (DTIC) has activity in advanced previously untreated pancreatic islet cell tumors [2]. In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75) [3].

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Nucleoside Antimetabolite/Analog

Research Areas >> Cancer

[References]

[1]. Serrone, L., et al., Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res, 2000. 19(1): p. 21-34.

[2]. Ramanathan, R.K., et al., Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Ann Oncol, 2001. 12(8): p. 1139-43.

[3]. Middleton, M.R., et al., Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol, 2000. 18(1): p. 158-66.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
456.3±55.0 °C at 760 mmHg

[ Melting Point ]:
199-205°C

[ Molecular Formula ]:
C₆H₁₀N₆O

[ Molecular Weight ]:
182.183

[ Flash Point ]:
229.7±31.5 °C

[ Exact Mass ]:
182.091614

[ PSA ]:
99.73000

[ LogP ]:
-0.28

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.678

[ Storage condition ]:
2-8°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NI3950000

CHEMICAL NAME :: Imidazole-4-carboxamide, 5-(3,3-dimethyl-1-triazeno)-

CAS REGISTRY NUMBER :: 4342-03-4

LAST UPDATED :: 199709

DATA ITEMS CITED :: 46

MOLECULAR FORMULA :: C6-H10-N6-O

MOLECULAR WEIGHT :: 182.22

WISWESSER LINE NOTATION :: T5M CNJ DVZ ENUNN1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 3500 ug/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting Blood - leukopenia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - dehydrogenases

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2147 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 350 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 411 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2032 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 567 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 466 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic

TYPE OF TEST :: LD10 - Lethal Dose

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 250 mg/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1568 mg/kg/14D-I

TOXIC EFFECTS :: Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1730 mg/kg/15W-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 25 mg/kg female 20 day(s) after conception

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - transplacental tumorigenesis Brain and Coverings - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3900 mg/kg/26W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1950 mg/kg/26W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3700 mg/kg/14W-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 50 mg/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 200 mg/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 100 mg/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 400 mg/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: DNA damage

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Mutation test systems - not otherwise specified

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: Mutation in mammalian somatic cells

TEST SYSTEM :: Rodent - hamster Ovary

DOSE/DURATION :: 400 mg/L

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 43,577,1983 *** REVIEWS *** IARC Cancer Review:Animal Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,203,1981 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,203,1981 IARC Cancer Review:Group 2B IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,184,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3246 No. of Facilities: 412 (estimated) No. of Industries: 1 No. of Occupations: 9 No. of Employees: 17273 (estimated) No. of Female Employees: 12863 (estimated)

Safety Information

[ Symbol ]:

GHS07, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302 + H312 + H332-H315-H319-H335-H340-H350

[ Precautionary Statements ]:
P201-P261-P280-P305 + P351 + P338-P308 + P313

[ Personal Protective Equipment ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
T:Toxic

[ Risk Phrases ]:
R45;R46;R20/21/22;R36/37/38

[ Safety Phrases ]:
S53-S36/37/39-S45

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
NI3950000

[ HS Code ]:
2933290090

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Direct chemosensitivity monitoring ex vivo on undissociated melanoma tumor tissue by impedance spectroscopy.

Cancer Res. 74(22) , 6408-18, (2014)

Stage III/IV melanoma remains incurable in most cases due to chemotherapeutic resistance. Thus, predicting and monitoring chemotherapeutic responses in this setting offer great interest. To overcome l...

Dacarbazine as a minor groove binder of DNA: Spectroscopic, biophysical and molecular docking studies.

Int. J. Biol. Macromol. 79 , 193-200, (2015)

A detailed investigation on the mode of action and binding mechanism of a potent anticancer drug, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DCR) with calf thymus DNA (ctDNA) was carried out...

A pro-apoptotic function of iASPP by stabilizing p300 and CBP through inhibition of BRMS1 E3 ubiquitin ligase activity.

Cell Death Dis. 6 , e1634, (2015)

The p53 family and its cofactors are potent inducers of apoptosis and form a barrier to cancer. Here, we investigated the impact of the supposedly inhibitory member of the apoptosis-stimulating protei...

Related Compounds

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