WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H100210
CAS#: 4342-03-4 (free base)
Description: Dacarbazine is a triazene derivative with antineoplastic activity. Dacarbazine alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis.
Hodoodo Cat#: H100210
Name: Dacarbazine
CAS#: 4342-03-4 (free base)
Chemical Formula: C6H10N6O
Exact Mass: 182.09
Molecular Weight: 182.180
Elemental Analysis: C, 39.56; H, 5.53; N, 46.13; O, 8.78
Related CAS #: 4342-03-4 (free base) 17925-90-5 (HCl) 64038-56-8 (citrate)
Synonym: WR139007; WR 139007; WR-139007; Biocarbazine; Dacarbazine; DTIC; Dakarbazin; US brand name: DTICDome. Foreign brand names: Asercit; Dacatic; Deticene; Detimedac; Fauldetic.
IUPAC/Chemical Name: (E)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-imidazole-4-carboxamide
InChi Key: FDKXTQMXEQVLRF-ZHACJKMWSA-N
InChi Code: 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+
SMILES Code: O=C(C1=C(/N=N/N(C)C)NC=N1)N
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Dacarbazine gained FDA approval in May 1975 as DTIC-Dome. The drug was initially marketed by Bayer. DTlC-Dome Sterile (dacarbazine) is a colorless to an ivory colored solid which is light sensitive. Each vial contains 100 mg of dacarbazine, or 200 mg of dacarbazine (the active ingredient), anhydrous citric acid and mannitol. DTlC-Dome is reconstituted and administered intravenously (pH 3–4). DTlC-Dome is an anticancer agent. DTlC-Dome is indicated in the treatment of metastatic malignant melanoma. In addition, DTlC-Dome is also indicated for Hodgkin's disease as a second-line therapy when used in combination with other effective agents. CLINICAL PHARMACOLOGY: After intravenous administration of DTlC-Dome, 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 DTlC in the urine is 40% of the injected dose in 6 hours.1 DTlC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations DTIC is not appreciably bound to human plasma protein. In man, DTlC is extensively degraded. Besides unchanged DTlC, 5-aminoimidazole -4 carboxamide (AlC) is a major metabolite of DTlC excreted in the urine. AlC is not derived endogenously but from the injected DTlC, because the administration of radioactive DTlC labeled with 14C in the imidazole portion of the molecule (DTlC-2-14C) gives rise to AIC-2-14C1. Although the exact mechanism of action of DTIC-Dome is not known, three hypotheses have been offered: 1. inhibition of DNA synthesis by acting as a purine analog 2. action as an alkylating agent 3. interaction with SH groups.
| Biological target: | Dacarbazine(DTIC-Dome; DTIC) is an antineoplastic agent that has significant activity against melanomas and targets nucleoside antimetabolite/analogs. |
| In vitro activity: | The aim of this study was to determine the influence of dacarbazine (DTIC) on morphology and kinetics of proliferation of B16 and Cloudman S91 cells. The Cloudman S91 cells after treatment with DTIC showed less anisocytosis when compared to B16 cells. The control samples revealed a low percentage of apoptotic and necrotic cells (Table 1). IC50 value of DTIC was 1.724 M for B16 cells and 2.920 M for Cloudman S91 cells (Figure 3). A significant diminution of B16 cell viability was found in these suspensions where dacarbazine concentration exceeded 1.373 M. The higher percentage of apoptotic B16 cells (11%) after 1.098 M DTIC exposure was identified (Table 1, Figure 4). Dacarbazine induces cell arrest in the G2/M and S phase in both lines (Figure 6D, E). A significant interaction of DTIC with B16 cells in the G2/M phase was observed. DTIC at concentration 1.647 M induced cell cycle arrest in 60% of B16 cells in G2/M phase (Table 2, Figure 6D). It is associated with drug concentration increase and this phenomenon was revealed also in the Cloudman S91 cell population (Figure 6E). An arrest of 37.5% Cloudman S91 cells in G2/M phase after treatment with 1.647 M DTIC was observed. The apoptosis process running in cell populations exposed to DTIC gives the knowledge which can be useful in finding out the appropriate dose for a cytostatic effect. Reference: Acta Pol Pharm. 2005 Nov-Dec;62(6):473-83. https://pubmed.ncbi.nlm.nih.gov/16583988/ |
| In vivo activity: | Wild-type or nude mice bearing a subcutaneous B16F10 melanoma tumor were first treated with DTIC (decarbazine). This treatment delayed tumor growth in wild-type mice but had no effect on tumor progression in nude mice, suggesting that the DTIC antitumor effect depends on T cells (Figure 1a). To further delineate the contribution of the host immune response to the anticancer effect of DTIC, tumor-bearing mice were treated with DTIC along with isotype or depleting anti-CD8, CD4, IFNγ, or NK1.1 antibodies to eliminate, respectively, CD8+ T cells (Figure 1b), CD4+ T cells (Figure 1c), IFNγ (Figure 1d), or NK cells (Figure 1e). Although CD4+ T cells were dispensable for DTIC therapeutic efficacy, it was found that the DTIC antitumor effect relied on CD8+ T cells, IFNγ, and NK cells. Interestingly, in NK- and IFNγ-depleted mice, the DTIC effect was totally abrogated, whereas in CD8+ T cell– depleted mice DTIC only exerted an early and transient effect on tumor progression, suggesting that NK cells and IFNγ, which act as early effectors against tumor progression, might subsequently trigger CD8+ T-cell activation. To further assess the immune-based effect of DTIC, mice were inoculated with 10 less B16F10 cells than usual and treated them according to the standard protocol. It was observed that in mice in which the low-dose tumor was implanted, the DTIC was more effective, suggesting a nontumor-based phenomenon (Figure 1f).Taken together, these data underscore the contribution of CD8+ T cells, IFNγ, and NK cells in the anticancer activity of DTIC. Reference: J Invest Dermatol. 2013 Feb;133(2):499-508. https://pubmed.ncbi.nlm.nih.gov/22951720/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 3.3 | 18.15 |
The following data is based on the product molecular weight 182.18 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Chen YN. Dacarbazine inhibits proliferation of melanoma FEMX-1 cells by up-regulating expression of miRNA-200. Eur Rev Med Pharmacol Sci. 2017 Mar;21(6):1191-1197. PMID: 28387914. 2. Olszewska-Słonina DM, Styczyńisk J, Drewa TA, Olszewski KJ, Czajkowski R. B16 and cloudman S91 mouse melanoma cells susceptibility to apoptosis after dacarbazine treatment. Acta Pol Pharm. 2005 Nov-Dec;62(6):473-83. PMID: 16583988. 3. Hervieu A, Rébé C, Végran F, Chalmin F, Bruchard M, Vabres P, Apetoh L, Ghiringhelli F, Mignot G. Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth. J Invest Dermatol. 2013 Feb;133(2):499-508. doi: 10.1038/jid.2012.273. Epub 2012 Sep 6. PMID: 22951720. 4. Winship AL, Bakai M, Sarma U, Liew SH, Hutt KJ. Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age. Sci Rep. 2018 Apr 25;8(1):6516. doi: 10.1038/s41598-018-24960-5. PMID: 29695822; PMCID: PMC5917018. |
| In vitro protocol: | 1. Chen YN. Dacarbazine inhibits proliferation of melanoma FEMX-1 cells by up-regulating expression of miRNA-200. Eur Rev Med Pharmacol Sci. 2017 Mar;21(6):1191-1197. PMID: 28387914. 2. Olszewska-Słonina DM, Styczyńisk J, Drewa TA, Olszewski KJ, Czajkowski R. B16 and cloudman S91 mouse melanoma cells susceptibility to apoptosis after dacarbazine treatment. Acta Pol Pharm. 2005 Nov-Dec;62(6):473-83. PMID: 16583988. |
| In vivo protocol: | 1.. Hervieu A, Rébé C, Végran F, Chalmin F, Bruchard M, Vabres P, Apetoh L, Ghiringhelli F, Mignot G. Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth. J Invest Dermatol. 2013 Feb;133(2):499-508. doi: 10.1038/jid.2012.273. Epub 2012 Sep 6. PMID: 22951720. 2. Winship AL, Bakai M, Sarma U, Liew SH, Hutt KJ. Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age. Sci Rep. 2018 Apr 25;8(1):6516. doi: 10.1038/s41598-018-24960-5. PMID: 29695822; PMCID: PMC5917018. |
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