Drug Details

General Information of the Drug (ID: DR0371)
Name
Dacarbazine
Synonyms
Biocarbazin; Biocarbazine; DTIC; DTICDome; DTIE; Dacarbazino; Dacarbazinum; Dacatic; Decarbazine; Deticene; Dimethyltriazenoimidazolecarboxamide; ICDMT; ICDT; Biocarbazine R; DTIC Dome; Dimethyl Imidazole Carboxamide; Dimethyl Triazeno Imidazole Carboxamide; Imidazole carboxamide; HE1150000; Carboxamide (TN); Carboxamide, Dimethyl Imidazole; DIC (TN); DTIC (TN); DTIC-Dome; Dacarbazino [INN-Spanish]; Dacarbazinum [INN-Latin]; Imidazole (TN); Imidazole Carboxamide, Dimethyl; NPFAPI-05; DTIC-Dome (TN); Di-me-triazenoimidazolecarboxamide; Di-methyl-triazenoimidazolecarboxamide; Dtic-Dome (TN); DTIC, DTIC-Dome, Dacarbazine; Dacarbazine (JAN/USP/INN); Dacarbazine [USAN:INN:BAN:JAN]; (5E)-5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide; (5Z)-5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide; (Dimethyltriazeno)imidazolecarboxamide; 4(5)-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide; 4(5)-(3,3-Dimethyl-1-triazeno)imidazole-5(4)-carboxamide; 4-(3,3-Dimethyl-1-triazeno)imidazole-5-carboxamide; 4-(3,3-Dimethyltriazeno)imidazole-5-carboxamide; 4-(5)-(3,3-Dimethyl-1-triazeno)imidazole-5(4)-carboxamide; 4-(Dimethyltriazeno)imidazole-5-c arboxamide; 4-(Dimethyltriazeno)imidazole-5-carboxamide; 4-(or 5)-(3,3-Dimethyl-1-triazeno)imidazole-5(or 4)-carboxamide; 4-[(1E)-3,3-Dimethyltriaz-1-en-1-yl]-1H-imidazole-5-carboxamide; 4-[3,3-dimethyltriaz-1-en-1-yl]-1H-imidazole-5-carboxamide; 5(or 4)-(dimethyltriazeno)imidazol e-4(or 5)-carboxamide; 5(or 4)-(dimethyltriazeno)imidazole-4(or 5)-carboxamide; 5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide; 5-(3,3-Dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide; 5-(3,3-Dimethyl-1-triazenyl)imidazole-4-carboxamide; 5-(3,3-Dimethyltri azeno)imidazole-4-carboxamide; 5-(3,3-Dimethyltriazeno)-imidazole-4-carbamide; 5-(3,3-Dimethyltriazeno)imidazole-4-carboxamide; 5-(3,3-dimethyltriaz-1-en-1-yl)-1H-imidazole-4-carboxamide; 5-(Dimethyltriazeno)-4-imidazolecarboxamide; 5-(Dimethyltriazeno)imidazole-4-carboxamide; 5-(Dimethyltriazeno)imidazole-4-carboximide; 5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide; 5-[3,3-Dimethyl-1-triazenyl]imidazole-4-carboxamide
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Molecular Type
Small molecule
Disease Melanoma [ICD-11: 2C30] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absorption
The drug is unstablely, slowly and incompletely absorbed
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability
Clearance
The drug present in the plasma can be removed from the body at the rate of 2.6 mL/min/kg
Elimination
39% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 5 hours
Metabolism
The drug is metabolized via the hepatic
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 24.7 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 1%
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.2 L/kg
Water Solubility
The ability of drug to dissolve in water is measured as 4.2 mg/mL
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C6H10N6O
PubChem CID
135398738
Canonical SMILES
CN(C)N=NC1=C(NC=N1)C(=O)N
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+
InChIKey
FDKXTQMXEQVLRF-ZHACJKMWSA-N
CAS Number
CAS 4342-03-4
ChEBI ID
CHEBI:4305
TTD Drug ID
D0Y7ZU
DrugBank ID
DB00851
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Epigallocatechin gallate      Hamamelis virginiana     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation FAK  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MMP-9  Molecule Info 
Pathway MAP
                    In-vitro Model B16 CVCL_F936 Mouse melanoma Mus musculus
                    In-vivo Model Animal models were constructed by injecting intraperitoneally B16-F3m cells (2*106) into Balb/c mice.
                    Experimental
                    Result(s)		 Combination treatment with EGCG and dacarbazine strongly inhibits melanoma growth and metastasis, and the action mechanisms of EGCG are associated with the inhibition of cell spreading, cell-extracellular matrix and cell-cell interactions, MMP-9 and FAK activities.
          Metformin      Galega officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression JNK2  Molecule Info 
Pathway MAP
                    In-vitro Model Raji CVCL_0511 EBV-related Burkitt lymphoma Homo sapiens
Ramos CVCL_0597 Burkitt lymphoma Homo sapiens
                    Experimental
                    Result(s)		 Metformin showed synergistic cytotoxic effects in combination with dacarbazine, reduced cell viability, and increased apoptosis in Raji and Ramos lymphoma cells in comparison with the use of each drug alone.
          Quercetin      Averrhoa carambola     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Increase Nuclear localization of deltaNp73
                    In-vitro Model DB1 CVCL_W884 Diffuse large B-cell lymphoma Homo sapiens
SK-MEL-28 CVCL_0526 Cutaneous melanoma Homo sapiens
                    Experimental
                    Result(s)		 Quercetin abrogates chemoresistance in melanoma cells by modulating deltaNp73.
          Vinblastine      Catharanthus roseus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 The results of the ECHELON-1 study showed a significantly longer modified progression-free survival (mPFS) following BV+AVD than with ABVD in primary HL.
Target and Pathway
Target(s) Human Deoxyribonucleic acid (hDNA)  Molecule Info  [6]
References
Reference 1 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075259.
Reference 2 Inhibition of melanoma growth and metastasis by combination with (-)-epigallocatechin-3-gallate and dacarbazine in mice. J Cell Biochem. 2001;83(4):631-42.
Reference 3 The Role of SAPK/JNK Pathway in the Synergistic Effects of Metformin and Dacarbazine on Apoptosis in Raji and Ramos Lymphoma Cells. Curr Mol Pharmacol. 2018;11(4):336-342.
Reference 4 Quercetin abrogates chemoresistance in melanoma cells by modulating deltaNp73. BMC Cancer. 2010 Jun 11;10:282.
Reference 5 Methotrexate-associated Hodgkin Lymphoma in a Patient with Rheumatoid Arthritis Successfully Treated with Brentuximab Vedotin in Combination with Doxorubicin, Vinblastine, and Dacarbazine (BV+AVD). Intern Med. 2020 Sep 1;59(17):2165-2171.
Reference 6 Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mono... Melanoma Res. 2011 Dec;21(6):502-8.
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