WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100210
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.
MedKoo Cat#: 100210
Chemical Formula: C6H10N6O
Exact Mass: 182.09161
Molecular Weight: 182.18
Elemental Analysis: C, 39.56; H, 5.53; N, 46.13; O, 8.78
Synonym: Biocarbazine; Dacarbazina; Dacarbazina Almirall; Dacarbazine DTIC; Dakarbazin; Dimethyl (triazeno) imidazolecarboxamide; Dimethyl Triazeno Imidazol Carboxamide; Dimethyl Triazeno Imidazole Carboxamide; Imidazole Carboxamide Imidazole Carboxamide Dimethyltriazeno; US brand name: DTICDome. Foreign brand names: Asercit; Dacatic; Deticene; Detimedac; Fauldetic. Abbreviations: DIC DTIC. Code name: WR139007.
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
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.
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.
1: Maafi M, Lee LY. Determination of Dacarbazine Φ-Order Photokinetics, Quantum Yields, and Potential for Actinometry. J Pharm Sci. 2015 Jul 14. doi: 10.1002/jps.24568. [Epub ahead of print] PubMed PMID: 26173629.
2: Shih V, Ten Ham RM, Bui CT, Tran DN, Ting J, Wilson L. Targeted Therapies Compared to Dacarbazine for Treatment of BRAF(V600E) Metastatic Melanoma: A Cost-Effectiveness Analysis. J Skin Cancer. 2015;2015:505302. doi: 10.1155/2015/505302. Epub 2015 Jun 10. PubMed PMID: 26171248; PubMed Central PMCID: PMC4478371.
3: Carvajal RD, Schwartz GK, Mann H, Smith I, Nathan PD. Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT). BMC Cancer. 2015 Jun 10;15:467. doi: 10.1186/s12885-015-1470-z. PubMed PMID: 26059332; PubMed Central PMCID: PMC4460965.
4: Latimer NR, Abrams KR, Amonkar MM, Stapelkamp C, Swann RS. Adjusting for the Confounding Effects of Treatment Switching-The BREAK-3 Trial: Dabrafenib Versus Dacarbazine. Oncologist. 2015 Jul;20(7):798-805. doi: 10.1634/theoncologist.2014-0429. Epub 2015 Jun 3. PubMed PMID: 26040620.
5: Urosevic-Maiwald M, Barysch MJ, Cheng PF, Karpova MB, Steinert H, Okoniewski MJ, Dummer R. In vivo profiling reveals immunomodulatory effects of sorafenib and dacarbazine on melanoma. Oncoimmunology. 2015 Jan 7;4(2):e988458. eCollection 2015 Feb. PubMed PMID: 25949886; PubMed Central PMCID: PMC4404845.
6: Ahmad I, Ahmad M. Dacarbazine as a minor groove binder of DNA: Spectroscopic, biophysical and molecular docking studies. Int J Biol Macromol. 2015 May 1;79:193-200. doi: 10.1016/j.ijbiomac.2015.04.055. [Epub ahead of print] PubMed PMID: 25940530.
7: Latosińska JN, Latosińska M, Seliger J, Žagar V, Burchardt DV, Derwich K. Unusual case of desmotropy. Combined spectroscopy (¹H-¹⁴N NQDR) and quantum chemistry (periodic hybrid DFT/QTAIM and Hirshfeld surface-based) study of solid dacarbazine (anti-neoplastic). Solid State Nucl Magn Reson. 2015 Jun-Jul;68-69:13-24. doi: 10.1016/j.ssnmr.2015.04.005. Epub 2015 Apr 23. PubMed PMID: 25936462.
8: Rozera C, Cappellini GA, D'Agostino G, Santodonato L, Castiello L, Urbani F, Macchia I, Aricò E, Casorelli I, Sestili P, Montefiore E, Monque D, Carlei D, Napolitano M, Rizza P, Moschella F, Buccione C, Belli R, Proietti E, Pavan A, Marchetti P, Belardelli F, Capone I. Intratumoral injection of IFN-alpha dendritic cells after dacarbazine activates anti-tumor immunity: results from a phase I trial in advanced melanoma. J Transl Med. 2015 May 2;13:139. doi: 10.1186/s12967-015-0473-5. PubMed PMID: 25933939; PubMed Central PMCID: PMC4438625.
9: Hardy KM, Strizzi L, Margaryan NV, Gupta K, Murphy GF, Scolyer RA, Hendrix MJ. Targeting nodal in conjunction with dacarbazine induces synergistic anticancer effects in metastatic melanoma. Mol Cancer Res. 2015 Apr;13(4):670-80. doi: 10.1158/1541-7786.MCR-14-0077. Epub 2015 Mar 12. PubMed PMID: 25767211; PubMed Central PMCID: PMC4398626.
10: Ferrucci PF, Minchella I, Mosconi M, Gandini S, Verrecchia F, Cocorocchio E, Passoni C, Pari C, Testori A, Coco P, Munzone E. Dacarbazine in combination with bevacizumab for the treatment of unresectable/metastatic melanoma: a phase II study. Melanoma Res. 2015 Jun;25(3):239-45. doi: 10.1097/CMR.0000000000000146. PubMed PMID: 25746039.