Dacarbazine | CAS#4342-03-4 | antineoplastic

MedKoo Cat#: 100210 | Name: Dacarbazine

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Dacarbazine

CAS#4342-03-4 (free base)

Theoretical Analysis

MedKoo Cat#: 100210

Name: Dacarbazine

CAS#: 4342-03-4 (free base)

Chemical Formula: C6H10N6O

Exact Mass: 182.0916

Molecular Weight: 182.18

Elemental Analysis: C, 39.56; H, 5.53; N, 46.13; O, 8.78

Price and Availability

Size	Price	Availability
100mg	USD 90.00	Ready to ship
200mg	USD 150.00	Ready to ship
500mg	USD 300.00	Ready to ship
1g	USD 450.00	Ready to ship
2g	USD 750.00	Ready to ship
5g	USD 1,450.00	Ready to ship

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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 3Â–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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#YYP30925

QC Data

View QC data: current batch, Lot#YYP30925

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	3.3	18.15

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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:

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.

1: Antonijevic NM, Zivkovic ID, Jovanovic LM, Matic DM, Kocica MJ, Mrdovic IB, Kanjuh VI, Culafic MD. Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions. Curr Drug Metab. 2017;18(7):622-635. doi: 10.2174/1389200218666170427113504. PMID: 28460624. 2: Paik J. Dabigatran Etexilate: A Review in Pediatric Venous Thromboembolism. Paediatr Drugs. 2022 Jul;24(4):423-431. doi: 10.1007/s40272-022-00516-z. Epub 2022 Jun 14. PMID: 35699915. 3: Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, Weitz JI. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med. 2017 Aug 3;377(5):431-441. doi: 10.1056/NEJMoa1707278. Epub 2017 Jul 11. PMID: 28693366. 4: Halton J, Brandão LR, Luciani M, Bomgaars L, Chalmers E, Mitchell LG, Nurmeev I, Sharathkumar A, Svirin P, Gorbatikov K, Tartakovsky I, Simetzberger M, Huang F, Sun Z, Kreuzer J, Gropper S, Reilly P, Brueckmann M, Albisetti M; DIVERSITY Trial Investigators. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol. 2021 Jan;8(1):e22-e33. doi: 10.1016/S2352-3026(20)30368-9. Epub 2020 Dec 5. PMID: 33290737. 5: Blair HA, Keating GM. Dabigatran Etexilate: A Review in Nonvalvular Atrial Fibrillation. Drugs. 2017 Mar;77(3):331-344. doi: 10.1007/s40265-017-0699-z. PMID: 28185082. 6: Brandão LR, Albisetti M, Halton J, Bomgaars L, Chalmers E, Mitchell LG, Nurmeev I, Svirin P, Kuhn T, Zapletal O, Tartakovsky I, Simetzberger M, Huang F, Sun Z, Kreuzer J, Gropper S, Brueckmann M, Luciani M; DIVERSITY Study Investigators. Safety of dabigatran etexilate for the secondary prevention of venous thromboembolism in children. Blood. 2020 Feb 13;135(7):491-504. doi: 10.1182/blood.2019000998. Erratum in: Blood. 2020 May 7;135(19):1720. PMID: 31805182; PMCID: PMC7019192. 7: Lin S, Wang Y, Zhang L, Guan W. Dabigatran must be used carefully: literature review and recommendations for management of adverse events. Drug Des Devel Ther. 2019 May 6;13:1527-1533. doi: 10.2147/DDDT.S203112. PMID: 31190734; PMCID: PMC6511609. 8: Vanassche T, Greinacher A, Verhamme P. Reversal of dabigatran by idarucizumab: when and how? Expert Rev Hematol. 2016 Jun;9(6):519-28. doi: 10.1080/17474086.2016.1184569. PMID: 27166653. 9: Kajihara Y. Dabigatran-induced esophagitis. Cleve Clin J Med. 2019 May;86(5):303-304. doi: 10.3949/ccjm.86a.18117. PMID: 31066667. 10: Ricca Gonçalves L, Robalo Nunes A. Reversão do Dabigatrano: Abordagem Prática [Dabigatran Reversal: A Practical Approach]. Acta Med Port. 2022 May 2;35(5):394-398. Portuguese. doi: 10.20344/amp.17662. Epub 2022 May 2. PMID: 36279894. 11: Syyed N, Ansell M, Sood V. Dabigatran (Pradaxa(®)): surgeon's friend or foe? Br Dent J. 2014 Dec 5;217(11):623-6. doi: 10.1038/sj.bdj.2014.1051. PMID: 25476635. 12: Enriquez A, Baranchuk A, Redfearn D, Simpson C, Abdollah H, Michael K. Dabigatran for the prevention and treatment of thromboembolic disorders. Expert Rev Cardiovasc Ther. 2015 May;13(5):529-40. doi: 10.1586/14779072.2015.1034692. Epub 2015 Apr 5. PMID: 25843430. 13: Drug interaction: dabigatran (Pradaxa) and statins. Med Lett Drugs Ther. 2017 Jan 30;59(1513):26. PMID: 28118653. 14: ten Cate H. Dabigatran and apolipoprotein B. Heart. 2016 Jan;102(1):5-6. doi: 10.1136/heartjnl-2015-308575. Epub 2015 Nov 13. PMID: 26567229; PMCID: PMC4717405. 15: Ng JW, Mohd Tahir NA, Chin PKL, Makmor-Bakry M, Mohd Saffian S. A systematic review and meta-analysis of dabigatran peak and trough concentration in adults. Br J Clin Pharmacol. 2022 Oct;88(10):4443-4459. doi: 10.1111/bcp.15431. Epub 2022 Jun 16. PMID: 35665523. 16: Shankar S, Saxena A, Saverimuthu A, Perez A, Chandar P, Shenoy MA, Seneviratne C, Kupfer Y. Dabigatran-Associated Diffuse Alveolar Hemorrhage. Am J Ther. 2020 May/Jun;27(3):e301-e303. doi: 10.1097/MJT.0000000000000816. PMID: 31567139. 17: Schellong SM. Dabigatran for the treatment of venous thromboembolism. Expert Rev Hematol. 2015 Aug;8(4):413-25. doi: 10.1586/17474086.2015.1052400. Epub 2015 Jun 25. PMID: 26111881. 18: Yogaratnam D, Ditch K, Medeiros K, Doyno C, Fong JJ. Idarucizumab for Reversal of Dabigatran-Associated Anticoagulation. Ann Pharmacother. 2016 Oct;50(10):847-54. doi: 10.1177/1060028016659504. Epub 2016 Jul 7. PMID: 27389324. 19: Siegal DM, Connolly SJ. Idarucizumab for Dabigatran-Related Gastrointestinal Bleeds. Circulation. 2019 Feb 5;139(6):757-759. doi: 10.1161/CIRCULATIONAHA.118.038460. PMID: 30715945. 20: Iwamuro M, Matsushita H, Tanaka T, Okada H. Dabigatran-induced esophagitis masking esophageal cancer. Dig Liver Dis. 2021 Feb;53(2):251-252. doi: 10.1016/j.dld.2020.05.019. Epub 2020 Jun 3. PMID: 32505570.