T3DB: Procarbazine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (1)XML

Targets (1)

Record Information

Version

2.0

Creation Date

2014-09-11 02:06:00 UTC

Update Date

2014-12-24 20:26:55 UTC

Accession Number

T3D4711

Identification

Common Name

Procarbazine

Class

Small Molecule

Description

Procarbazine 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

MOL SDF PDB SMILES InChI

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 Formula

C₁₂H₁₉N₃O

Average Molecular Mass

221.299 g/mol

Monoisotopic Mass

221.153 g/mol

CAS Registry Number

671-16-9

IUPAC Name

4-[(2-methylhydrazin-1-yl)methyl]-N-(propan-2-yl)benzamide

Traditional Name

procarbazine

SMILES

CNNCC1=CC=C(C=C1)C(=O)NC(C)C

InChI Identifier

InChI=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 Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Benzoic acids and derivatives

Direct Parent

Benzamides

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 Framework

Aromatic homomonocyclic compounds

External Descriptors

benzamides (CHEBI:71417 )
hydrazines (CHEBI:71417 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	223°C
Boiling Point	Not Available
Solubility	1420 mg/L
LogP	0.06

Predicted Properties

Property	Value	Source
Water Solubility	0.23 g/L	ALOGPS
logP	0.53	ALOGPS
logP	0.99	ChemAxon
logS	-3	ALOGPS
pKa (Strongest Acidic)	15.03	ChemAxon
pKa (Strongest Basic)	5.6	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	53.16 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	86.98 m³·mol⁻¹	ChemAxon
Polarizability	25.88 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-07c6-7920000000-3801345089023dd56325	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0096-0910000000-161c214dc9eb9c75895b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-0007-1900000000-60a80240bc36c4e7800c	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-1960000000-9fa182eac5a77441bb8a	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03fr-0900000000-ff9288484ea9ffb99146	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a59-2900000000-bc0369114d1004e57e00	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00dl-5890000000-78c039ed3aeb234794ac	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00fs-9540000000-bbeb52cfbb2f51e65f4a	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a6s-9300000000-ff5f840e133b25fca3e8	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0490000000-b3cffe9991e860361d01	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0006-5910000000-82dbcdbeb00d6d699efe	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00kf-9800000000-b4a3ffc75a2a54dec41d	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0090000000-c9adb40f1d12198563b4	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00dl-7890000000-322337f6eb79ffbcde5a	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0f6x-7900000000-eb93f2bc78bb4992e059	2021-10-11	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-016u-6900000000-6488b097a4640e8af61a	2014-09-20	View Spectrum

Toxicity Profile

Route of Exposure

Procarbazine is rapidly and completely absorbed.

Mechanism of Toxicity

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.

Metabolism

Procarbazine 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 Values

LD₅₀=785 mg/kg (orally in rats)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

Procarbazine is part of MOPP, a combination chemotherapy regimen that is carcinogenic to humans (Group 1). (1)

Uses/Sources

For use with other anticancer drugs for the treatment of stage III and stage IV Hodgkin's disease.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

366225

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Procarbazine

References

Synthesis Reference

DrugSyn.org

MSDS

Link

General References

International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not 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

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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 ]
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 ]
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 ]

Procarbazine (T3D4711)

Structure for T3D4711: Procarbazine

Targets

References