Identification
- Summary
Procarbazine is an antineoplastic agent indicated for the treatment of stage III and stage IV Hodgkin's disease in combination with other chemotherapeutic agents.
- Brand Names
- Matulane
- Generic Name
- Procarbazine
- DrugBank Accession Number
- DB01168
- Background
An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Procarbazine (DB01168)
- Weight
- Average: 221.2988
Monoisotopic: 221.152812245 - Chemical Formula
- C12H19N3O
- Synonyms
- 1-Methyl-2-(p-(isopropylcarbamoyl)benzyl)hydrazine
- 2-(p-Isopropylcarbamoylbenzyl)-1-methylhydrazine
- 4-((2-Methylhydrazino)methyl)-N-isopropylbenzamide
- N-(1-Methylethyl)-4-((2-methylhydrazino)methyl)benzamide
- N-4-Isopropylcarbamoylbenzyl-N'-methylhydrazine
- N-isopropyl-4-[(2-methylhydrazino)methyl]benzamide
- N-Isopropyl-p-(2-methylhydrazinomethyl)-benzamide
- N-Isopropyl-α-(2-methylhydrazino)-p-toluamide
- p-(2-Methylhydrazinomethyl)-N-isopropylbenzamide
- Procarbazin
- Procarbazina
- Procarbazine
- Procarbazinum
- External IDs
- RO-4-6467
Pharmacology
- Indication
For use with other anticancer drugs for the treatment of stage III and stage IV Hodgkin's disease.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Non-hodgkin lymphoma ••• ••••• Treatment of Oligodendroglioma ••• ••••• Treatment of Primary cns lymphoma ••• ••••• Used in combination to treat Stage 3 hodgkin's disease Regimen in combination with: Prednisone (DB00635), Vincristine (DB00541), Mechlorethamine (DB00888) •••••••••••• Used in combination to treat Stage 4 hodgkin's disease Regimen in combination with: Vincristine (DB00541), Prednisone (DB00635), Mechlorethamine (DB00888) •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Procarbazine is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Procarbazine is cell-phase specific for the S phase of cell division.
- Mechanism of action
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.
Target Actions Organism AMonoamine oxidase inhibitorHumans ADNA cross-linking/alkylationHumans - Absorption
Procarbazine is rapidly and completely absorbed.
- Volume of distribution
Not Available
- Protein binding
Not Available
- 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.
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- Route of elimination
Not Available
- Half-life
10 minutes
- Clearance
Not Available
- Adverse Effects
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LD50=785 mg/kg (orally in rats)
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Procarbazine is combined with 1,2-Benzodiazepine. Abaloparatide Procarbazine may increase the orthostatic hypotensive activities of Abaloparatide. Abatacept The risk or severity of adverse effects can be increased when Procarbazine is combined with Abatacept. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Procarbazine is combined with Abciximab. Acarbose Procarbazine may increase the hypoglycemic activities of Acarbose. - Food Interactions
- Avoid alcohol. Ingesting alcohol may potentiate the CNS depressant effects of procarbazine and may precipitate a disulfiram-like-reaction (nausea, flushing).
- Avoid tyramine-containing foods and supplements. Foods that contain tyramine include yogurt, aged cheese, ripe bananas, wine, and sourdough bread.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Procarbazine hydrochloride XH0NPH5ZX8 366-70-1 OCSSHHHAHMCFDV-UHFFFAOYSA-N - International/Other Brands
- Indicarb / Natulan
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Matulane Capsule 50 mg Oral Leadiant Biosciences, Inc 1970-12-31 Not applicable Canada 
Matulane Capsule 50 mg/1 Oral Sigma-Tau Pharmaceuticals, Inc. 1985-12-27 2020-03-31 US 
Matulane Capsule 50 mg/1 Oral Leadiant Biosciences, Inc. 1985-12-27 Not applicable US
Categories
- ATC Codes
- L01XB01 — Procarbazine
- Drug Categories
- Acids, Carbocyclic
- Agents Causing Muscle Toxicity
- Alkylating Activity
- Alkylating Drugs
- Amides
- Antidepressive Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Benzamides and benzamide derivatives
- Benzene Derivatives
- Benzoates
- Central Nervous System Depressants
- Immunosuppressive Agents
- Methylhydrazines
- Monoamine Oxidase Inhibitors
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin Modulators
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound 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
- Benzoyl derivatives / Secondary carboxylic acid amides / Alkylhydrazines / Organopnictogen compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- Alkylhydrazine / Aromatic homomonocyclic compound / Benzamide / Benzoyl / Carboxamide group / Carboxylic acid derivative / Hydrazine derivative / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- benzamides, hydrazines (CHEBI:71417)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 35S93Y190K
- CAS number
- 671-16-9
- InChI Key
- CPTBDICYNRMXFX-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 4-[(2-methylhydrazin-1-yl)methyl]-N-(propan-2-yl)benzamide
- SMILES
- CNNCC1=CC=C(C=C1)C(=O)NC(C)C
References
- Synthesis Reference
- US3520926
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015299
- KEGG Drug
- D08423
- KEGG Compound
- C07402
- PubChem Compound
- 4915
- PubChem Substance
- 46507706
- ChemSpider
- 4746
- 8702
- ChEBI
- 71417
- ChEMBL
- CHEMBL1321
- ZINC
- ZINC000019166988
- Therapeutic Targets Database
- DAP000986
- PharmGKB
- PA451112
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Procarbazine
- MSDS
- Download (63.2 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Lymphoma 5 3 Completed Treatment Advanced Hodgkin Disease 1 3 Completed Treatment Brain and Central Nervous System Tumors 4 3 Completed Treatment Brain Neoplasm / Central Nervous System Neoplasm 1 3 Completed Treatment Hodgkin's Lymphoma 5
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- AAIPharma Inc.
- B&B Pharmaceuticals
- Kaiser Foundation Hospital
- Sigma-Tau Pharmaceuticals Inc.
- Dosage Forms
Form Route Strength Capsule Oral 50 mg/1 Capsule Oral 50 mg - Prices
Unit description Cost Unit Matulane 50 mg capsule 55.68USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 223 °C Not Available water solubility 1420 mg/L Not Available logP 0.06 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.228 mg/mL ALOGPS logP 0.53 ALOGPS logP 0.99 Chemaxon logS -3 ALOGPS pKa (Strongest Acidic) 15.03 Chemaxon pKa (Strongest Basic) 5.56 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 No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9954 Blood Brain Barrier + 0.9855 Caco-2 permeable + 0.6013 P-glycoprotein substrate Non-substrate 0.5748 P-glycoprotein inhibitor I Non-inhibitor 0.8839 P-glycoprotein inhibitor II Non-inhibitor 0.9771 Renal organic cation transporter Non-inhibitor 0.7974 CYP450 2C9 substrate Non-substrate 0.8293 CYP450 2D6 substrate Non-substrate 0.702 CYP450 3A4 substrate Non-substrate 0.5484 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Non-inhibitor 0.8308 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9414 Ames test Non AMES toxic 0.9132 Carcinogenicity Carcinogens 0.6428 Biodegradation Not ready biodegradable 0.9741 Rat acute toxicity 2.4348 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9785 hERG inhibition (predictor II) Non-inhibitor 0.9287
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 172.1841184 predictedDarkChem Lite v0.1.0 [M-H]- 150.8351 predictedDeepCCS 1.0 (2019) [M+H]+ 172.4027184 predictedDarkChem Lite v0.1.0 [M+H]+ 153.23065 predictedDeepCCS 1.0 (2019) [M+Na]+ 171.7307184 predictedDarkChem Lite v0.1.0 [M+Na]+ 159.27843 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Components:
References
- Holt A, Sharman DF, Callingham BA, Kettler R: Characteristics of procarbazine as an inhibitor in-vitro of rat semicarbazide-sensitive amine oxidase. J Pharm Pharmacol. 1992 Jun;44(6):487-93. [Article]
- Kraft SL, Baker NM, Carpenter J, Bostwick JR: Procarbazine and antidepressants: a retrospective review of the risk of serotonin toxicity. Psychooncology. 2014 Jan;23(1):108-13. doi: 10.1002/pon.3378. Epub 2013 Aug 29. [Article]
Yes
Cross-linking/alkylation
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xanthine oxidase activity
- Specific Function
- Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
- Gene Name
- XDH
- Uniprot ID
- P47989
- Uniprot Name
- Xanthine dehydrogenase/oxidase
- Molecular Weight
- 146422.99 Da
References
- Tweedie DJ, Fernandez D, Spearman ME, Feldhoff RC, Prough RA: Metabolism of azoxy derivatives of procarbazine by aldehyde dehydrogenase and xanthine oxidase. Drug Metab Dispos. 1991 Jul-Aug;19(4):793-803. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54