Tmic
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Record Information
Version2.0
Creation Date2014-09-11 02:06:00 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4711
Identification
Common NameProcarbazine
ClassSmall Molecule
DescriptionProcarbazine is only found in individuals that have used or taken this drug. It is an antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease. The precise mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the drug, may attack protein sulfhydryl groups contained in residual protein which is tightly bound to DNA.
Compound Type
  • Amide
  • Amine
  • Antineoplastic Agent
  • Drug
  • Ester
  • Hydrazine
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1-Methyl-2-(P-(isopropylcarbamoyl)benzyl)hydrazine
2-(P-Isopropylcarbamoylbenzyl)-1-methylhydrazine
4-((2-Methylhydrazino)methyl)-N-isopropylbenzamide
Ibenzmethyzin
Ibenzmethyzine
IBZ
Indicarb
Matulane
MBH
MIH
N-(1-Methylethyl)-4-((2-methylhydrazino)methyl)benzamide
N-4-Isopropylcarbamoylbenzyl-n'-methylhydrazine
N-Isopropyl-4-[(2-methylhydrazino)methyl]benzamide
N-Isopropyl-alpha-(2-methylhydrazino)-P-toluamide
N-Isopropyl-P-(2-methylhydrazinomethyl)-benzamide
Natulan
P-(2-Methylhydrazinomethyl)-N-isopropylbenzamide
PCX
Procarbazin
Procarbazina
Procarbazinum
Chemical FormulaC12H19N3O
Average Molecular Mass221.299 g/mol
Monoisotopic Mass221.153 g/mol
CAS Registry Number671-16-9
IUPAC Name4-[(2-methylhydrazin-1-yl)methyl]-N-(propan-2-yl)benzamide
Traditional Nameprocarbazine
SMILESCNNCC1=CC=C(C=C1)C(=O)NC(C)C
InChI IdentifierInChI=1S/C12H19N3O/c1-9(2)15-12(16)11-6-4-10(5-7-11)8-14-13-3/h4-7,9,13-14H,8H2,1-3H3,(H,15,16)
InChI KeyInChIKey=CPTBDICYNRMXFX-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentBenzamides
Alternative Parents
Substituents
  • Benzamide
  • Benzoyl
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Alkylhydrazine
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrazine derivative
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point223°C
Boiling PointNot Available
Solubility1420 mg/L
LogP0.06
Predicted Properties
PropertyValueSource
Water Solubility0.23 g/LALOGPS
logP0.53ALOGPS
logP0.99ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)15.03ChemAxon
pKa (Strongest Basic)5.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area53.16 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity86.98 m³·mol⁻¹ChemAxon
Polarizability25.88 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-07c6-7920000000-3801345089023dd56325View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0096-0910000000-161c214dc9eb9c75895bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-1960000000-9fa182eac5a77441bb8aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03fr-0900000000-ff9288484ea9ffb99146View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a59-2900000000-bc0369114d1004e57e00View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00dl-5890000000-78c039ed3aeb234794acView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00fs-9540000000-bbeb52cfbb2f51e65f4aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a6s-9300000000-ff5f840e133b25fca3e8View in MoNA
MSMass Spectrum (Electron Ionization)splash10-016u-6900000000-6488b097a4640e8af61aView in MoNA
Toxicity Profile
Route of ExposureProcarbazine is rapidly and completely absorbed.
Mechanism of ToxicityThe precise mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the drug, may attack protein sulfhydryl groups contained in residual protein which is tightly bound to DNA.
MetabolismProcarbazine is metabolized primarily in the liver and kidneys. The drug appears to be auto-oxidized to the azo derivative with the release of hydrogen peroxide. The azo derivative isomerizes to the hydrazone, and following hydrolysis splits into a benzylaldehyde derivative and methylhydrazine. The methylhydrazine is further degraded to CO2 and CH4 and possibly hydrazine, whereas the aldehyde is oxidized to N-isopropylterephthalamic acid, which is excreted in the urine. Half Life: 10 minutes
Toxicity ValuesLD50=785 mg/kg (orally in rats)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Procarbazine is part of MOPP, a combination chemotherapy regimen that is carcinogenic to humans (Group 1). (1)
Uses/SourcesFor use with other anticancer drugs for the treatment of stage III and stage IV Hodgkin's disease.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01168
HMDB IDHMDB15299
PubChem Compound ID4915
ChEMBL IDCHEMBL1321
ChemSpider ID4746
KEGG IDC07402
UniProt IDNot Available
OMIM ID
ChEBI ID366225
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkProcarbazine
References
Synthesis Reference

DrugSyn.org

MSDSLink
General References
  1. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Ogawa K, Hiraku Y, Oikawa S, Murata M, Sugimura Y, Kawamura J, Kawanishi S: Molecular mechanisms of DNA damage induced by procarbazine in the presence of Cu(II). Mutat Res. 2003 Aug 5;539(1-2):145-55. [12948823 ]
  4. Kyrtopoulos SA, Anderson LM, Chhabra SK, Souliotis VL, Pletsa V, Valavanis C, Georgiadis P: DNA adducts and the mechanism of carcinogenesis and cytotoxicity of methylating agents of environmental and clinical significance. Cancer Detect Prev. 1997;21(5):391-405. [9307842 ]