U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C12H19N3O
Molecular Weight 221.2992
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROCARBAZINE

SMILES

CC(C)NC(=O)c1ccc(cc1)CNNC

InChI

InChIKey=CPTBDICYNRMXFX-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/4360491 | https://www.ncbi.nlm.nih.gov/pubmed/10944597 | https://clinicaltrials.gov/ct2/show/NCT02800447 | https://clinicaltrials.gov/ct2/show/NCT01737346

Procarbazine is a chemotherapy medication used for the treatment of Hodgkin's lymphoma and brain cancers. For Hodgkin's it is often used together with mechlorethamine, vincristine, and prednisone while for brain cancers such as glioblastoma multiforme it is used with lomustine and vincristine. Procarbazine inhibits DNA, RNA, and protein synthesis by inhibiting transmethylation of methionine into transfer RNA; may also damage DNA directly through alkylation. Common side effect include low blood cell counts and vomiting. Other side effects include tiredness and depression.

CNS Activity

Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/28321136

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MATULANE

Approved Use

Matulane is indicated for use in combination with other anticancer drugs for the treatment of Stage III and IV Hodgkin's disease. Matulane is used as part of the MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) regimen.

Launch Date

-1.40832E10
Primary
MATULANE

Approved Use

Matulane is indicated for use in combination with other anticancer drugs for the treatment of Stage III and IV Hodgkin's disease. Matulane is used as part of the MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) regimen.

Launch Date

-1.40832E10
Primary
MATULANE

Approved Use

Matulane is indicated for use in combination with other anticancer drugs for the treatment of Stage III and IV Hodgkin's disease. Matulane is used as part of the MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) regimen.

Launch Date

-1.40832E10
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.692 μg/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROCARBAZINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
0.217 μg × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROCARBAZINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.154 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROCARBAZINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (grade 3-4, 3%)
Vomiting (grade 3-4, 5%)
Fatigue (grade 3-4, 2%)
Constipation (grade 3-4, 1%)
Anorexia (grade 3-4, 2%)
Headache (grade 3-4, 2%)
Rash (grade 3-4, 1%)
Thrombocytopenia (grade 3-4, 4%)
Neutropenia (grade 3-4, 3%)
Anemia (grade 3-4, 2%)
Diarrhea (grade 3-4, 1%)
Sources: Page: p.593
AEs

AEs

AESignificanceDosePopulation
Constipation grade 3-4, 1%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Diarrhea grade 3-4, 1%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Rash grade 3-4, 1%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Anemia grade 3-4, 2%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Anorexia grade 3-4, 2%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Fatigue grade 3-4, 2%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Headache grade 3-4, 2%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Nausea grade 3-4, 3%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Neutropenia grade 3-4, 3%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Thrombocytopenia grade 3-4, 4%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
Vomiting grade 3-4, 5%
150 mg/m2 1 times / day multiple, intravenous (max)
Highest studied dose
Dose: 150 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 150 mg/m2, 1 times / day
Sources: Page: p.593
unhealthy, 21–74
n = 113
Health Status: unhealthy
Condition: Glioblastoma multiforme
Age Group: 21–74
Sex: M+F
Population Size: 113
Sources: Page: p.593
PubMed

PubMed

TitleDatePubMed
The immunosuppressive activity of procarbazine hydrochloride in canine renal allografts by donor pretreatment.
1972
Severe cerebral toxicity after intravenous nitrogen mustard therapy.
1972 Feb
Central nervous system disturbances after combined administration of procarbazine and mechlorethamine.
1977 Dec
Action of N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide hydrochloride (procarbazine hydrochloride) in the germ tissue of mice: dominant lethal effects.
1979 Feb 23
BCVPP chemotherapy for advanced Hodgkin's disease: evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen. Results of the Eastern Cooperative Oncology Group study.
1984 Oct
Procarbazine is a potent mutagen at the heterozygous thymidine kinase (tk +/-) locus of mouse lymphoma assay.
1988 Mar
Cyclophosphamide-associated carcinoma of urothelium: modalities for prevention.
1991 Nov
A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy.
1992 Oct
Alteration of mRNA transcript levels of rat testicular cells following procarbazine administration.
1993 Jul-Aug
Aplastic anemia induced by cyclohexylchloroethylnitrousurea.
1994 Feb
Further studies on the ex-vivo effects of procarbazine and monomethylhydrazine on rat semicarbazide-sensitive amine oxidase and monoamine oxidase activities.
1995 Oct
Therapy-related leukemia with a novel 21q22 rearrangement.
1996 Aug
An update of the National Toxicology Program database on nasal carcinogens.
1997 Oct 31
Identification of mammary carcinogens in rodent bioassays.
2002
Molecular mechanisms of DNA damage induced by procarbazine in the presence of Cu(II).
2003 Aug 5
Neuropsychological outcome in children with optic pathway tumours when first-line treatment is chemotherapy.
2003 Dec 1
[Clinical study of Hodgkin's disease after 25 years].
2004
Molecular genetic study of a metastatic oligodendroglioma.
2004 Feb
Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study.
2004 Feb 10
[Action of Natulan in 94 solid tumours. 1966].
2004 Sep
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Secondary transitional cell carcinoma and nitrogen mustard treatment.
2005 Jun
[Ten-year outcomes of lymphogranulomatosis treatment according to the protocol MOPP-ABVD+radiotherapy].
2006
Policy challenges for cancer research: a call to arms.
2007
Targeted brain tumor treatment-current perspectives.
2007
Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial.
2007 Aug 10
Defeating cancer with antidepressants.
2008
Cerebellar dysfunction caused by procarbazine and consumption of excessive amount of bananas.
2008 Jun
NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide.
2009 Dec 10
Recurrent high-grade glioma.
2010 Jul
Alpha-internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy: European organization for research and treatment of cancer trial 26951.
2011 Jul 1
NOA-05 phase 2 trial of procarbazine and lomustine therapy in gliomatosis cerebri.
2011 Sep
Patents

Sample Use Guides

To minimize the nausea and vomiting experienced by a high percentage of patients beginning procarbazine therapy, single or divided doses of 2 to 4 mg/kg/day for the first week are recommended. Daily dosage should then be maintained at 4 to 6 mg/kg/day until maximum response is obtained or until the white blood count falls below 4000 or the platelets fall below 100,000. When maximum response is obtained, the dose may be maintained at 1 to 2 mg/kg/day. Upon evidence of hematologic or other toxicity, the drug should be discontinued until there has been satisfactory recovery. After toxic side effects have subsided, therapy may then be resumed at the discretion of the physician, based on clinical evaluation and appropriate laboratory studies, at a dosage of 1 to 2 mg/kg/day.
Route of Administration: Oral
In Vitro Use Guide
LI210 cells growing in log phase were collected by centrifugation and were resuspended in complete media containing 1% horse serum and 100 U/ml penicillin and 100 ng/ml streptomycin at 3 x IO6cells/ml. After a 10-min preincubation period at 37°C,either procarbazine or one of its various metabolites were added in ethanol (<50 ^1/ml media); control cells received an equal volume of ethanol alone. The treatment was carried out in a COz incubator and tubes were gently shaken every 10 min. After incubation, 5 ml of ice-cold Dulbecco's phosphatebuffered salt solution (pH 7.4) was added to each tube and the cells pelleted as above. The wash step was repeated and cells resuspended in Dulbecco's phosphate-buffered salt solution at a cell concentration of 1 x 106/ml. When alkaline-elution analysis was performed, cells were held on ice for up to 1 h to inhibit cellular repair processes prior to analysis. When growth experiments were performed, cells were resus pended in regular culture media containing antibiotics and allowed to reestablish growth.
Name Type Language
PROCARBAZINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
PROCARBAZINE [WHO-DD]
Common Name English
PROCARBAZINE [MI]
Common Name English
N-4-ISOPROPYLCARBAMOYLBENZYL-N'-METHYLHYDRAZINE
Systematic Name English
RO-4-6467 FREE BASE
Code English
N-ISOPROPYL-A-(2-METHYLHYDRAZINO)-P-TOLUAMIDE
Systematic Name English
PROCARBACINE
Common Name English
PROCARBAZINE [HSDB]
Common Name English
N-ISOPROPYL-.ALPHA.-(2-METHYLHYDRAZINO)-P-TOLUAMIDE
Systematic Name English
PROCARBAZINE [VANDF]
Common Name English
RO-4-6467
Code English
PROCARBAZINE [INN]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175558
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
NDF-RT N0000000236
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
NCI_THESAURUS C902
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
LIVERTOX 801
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
WHO-VATC QL01XB01
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 8.2
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
WHO-ATC L01XB01
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
Code System Code Type Description
INN
2147
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
DRUG CENTRAL
2272
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
RXCUI
8702
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY RxNorm
FDA UNII
35S93Y190K
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
NCI_THESAURUS
C62072
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
EVMPD
SUB10057MIG
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
CAS
671-16-9
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
HSDB
3250
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
DRUG BANK
DB01168
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
MESH
D011344
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
WIKIPEDIA
PROCARBAZINE
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
EPA CompTox
671-16-9
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
IUPHAR
7278
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
MERCK INDEX
M9146
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL1321
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
ECHA (EC/EINECS)
211-582-2
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY
PUBCHEM
4915
Created by admin on Sat Jun 26 14:49:53 UTC 2021 , Edited by admin on Sat Jun 26 14:49:53 UTC 2021
PRIMARY