WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100760
CAS#: 366-70-1 (HCl)
Description: Procarbazine is an antineoplastic chemotherapy drug for the treatment of Hodgkin's lymphoma and certain brain cancers (such as glioblastoma multiforme). It is a member of a group of medicines called alkylating agents. The drug is metabolized and activated in the liver. It also inhibits MAO thus increasing the effects of sympathomimetics, TCAs, and tyramine. It gained FDA Approved in July 1969. It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
MedKoo Cat#: 100760
Name: Procarbazine HCl
CAS#: 366-70-1 (HCl)
Chemical Formula: C12H20ClN3O
Exact Mass: 221.15281
Molecular Weight: 257.76
Elemental Analysis: C, 55.92; H, 7.82; Cl, 13.75; N, 16.30; O, 6.21
Synonym: CB 400-497; NSC-77213; Ro 4-6467; Ro 4-6467/1; Procarbazine Hydrochloride; PCB Hydrochloride; PCZ; Procarbazin. Matulane. Natulan; Natulanar; Natunalar.
IUPAC/Chemical Name: N-isopropyl-4-((2-methylhydrazinyl)methyl)benzamide hydrochloride
InChi Key: DERJYEZSLHIUKF-UHFFFAOYSA-N
InChi Code: InChI=1S/C12H19N3O.ClH/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);1H
SMILES Code: O=C(NC(C)C)C1=CC=C(CNNC)C=C1.[H]Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Procarbazine Hydrochloride is an alkylating agent, with anticancer activity.|
|In vitro activity:||Electron spin resonance (ESR) analysis combined with the use of 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) and dibromonitroso benzenesulfonic acid (DBNBS) as spin-trapping agents was used to characterize free radical generation during the metabolism of the anticancer agent procarbazine [N-isopropyl-a-(2-methylhydrazino)-p-toluamide hydrochloride]. The formation of free radical species, identified as methyl radicals, was observed during oxidation of procarbazine in rat liver microsomes and isolated hepatocytes in vitro. The metabolic pathway leading to free radical formation was characterized using various procarbazine metabolites and revealed strict analogies with previously published data on methane production from procarbazine. These results supported the identification of the trapped species as methyl free radical and suggested that C-oxidation of azoprocarbazine is the main source of radical intermediates derived from this anticancer drug. Reference: Carcinogenesis. 1992 May;13(5):799-805. https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/13.5.799|
|In vivo activity:||Flow cytometry-based erythrocyte and T lymphocyte assays were employed in order to quantify the frequencies of cells deficient in glycosylphosphatidyl inositol-anchored surface markers CD59 and CD48 (presumed mutants in the endogenous X-linked Pig-a gene) in rats. The rats were treated once daily with 100 mg/kg procarbazine HCl for 3 days. In addition, we sorted mutant-phenotype spleen T cells and immediately analysed their Pig-a gene using next generation sequencing of dual-indexed multiplex libraries and error-correcting data filtering. More than 100-fold increase in the frequencies of CD59-deficient RBCs was observed at Day 29 after the last administration, and a 10-fold increase in the frequency of CD48-deficient T cells was observed at Days 45 to 50. Sequencing revealed that, in T cells from procarbazine-treated rats, mutations in the Pig-a gene occurred predominantly at A:T basepairs when A was located on the non-transcribed DNA strand. A→T transversion was the most common mutation. The results suggest that, at least for the transcribed X-linked Pig-a gene, in vivo methyl guanine adducts are not the major contributors to mutations induced by procarbazine. Reference: Mutagenesis. 2017 Dec 31;32(6):571-579. https://academic.oup.com/mutage/article-lookup/doi/10.1093/mutage/gex032|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 257.76 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||1. Goria-Gatti L, Iannone A, Tomasi A, Poli G, Albano E. In vitro and in vivo evidence for the formation of methyl radical from procarbazine: a spin-trapping study. Carcinogenesis. 1992 May;13(5):799-805. doi: 10.1093/carcin/13.5.799. PMID: 1316811.|
|In vivo protocol:||1. Revollo J, Bhalli JA, Tebbe C, Noteboom J, Thomas D, McKinzie P, Felton N, Pearce MG, Dobrovolsky VN. Spectrum of Pig-a mutations in T lymphocytes of rats treated with procarbazine. Mutagenesis. 2017 Dec 31;32(6):571-579. doi: 10.1093/mutage/gex032. PMID: 29237063. 2. Maurice C, Dertinger SD, Yauk CL, Marchetti F. Integrated In Vivo Genotoxicity Assessment of Procarbazine Hydrochloride Demonstrates Induction of Pig-a and LacZ Mutations, and Micronuclei, in MutaMouse Hematopoietic Cells. Environ Mol Mutagen. 2019 Jul;60(6):505-512. doi: 10.1002/em.22271. Epub 2019 Jan 18. PMID: 30592561; PMCID: PMC6618172.|
1: Yap KY, Tay WL, Chui WK, Chan A. Clinically relevant drug interactions between anticancer drugs and psychotropic agents. Eur J Cancer Care (Engl). 2009 Dec 17. [Epub ahead of print] PubMed PMID: 20030690.
2: Roos WP, Nikolova T, Quiros S, Naumann SC, Kiedron O, Zdzienicka MZ, Kaina B. Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations by a process leading to SCEs. DNA Repair (Amst). 2009 Jan 1;8(1):72-86. Epub 2008 Oct 21. PubMed PMID: 18840549.
3: Ribrag V, Koscielny S, Casasnovas O, Cazeneuve C, Brice P, Morschhauser F, Gabarre J, Stamatoullas A, Lenoir G, Salles G; Groupe d'Etude des Lymphomes agressifs group, Laboratoire de GÃ©nÃ©tique et de recherche translationnelle, and Institut Gustave Roussy. Pharmacogenetic study in Hodgkin lymphomas reveals the impact of UGT1A1 polymorphisms on patient prognosis. Blood. 2009 Apr 2;113(14):3307-13. Epub 2008 Sep 3. PubMed PMID: 18768784.
4: Krawczuk-Rybak M, Leszczyńska E, Wysocka J, Zelazowska-Rutkowska B. [Anti-mullerian hormone in young women after chemotherapy and infradiaphragmatic radiotherapy for childhood cancer]. Pediatr Endocrinol Diabetes Metab. 2008;14(2):99-103. Polish. PubMed PMID: 18721496.
5: Glen CD, Smith AG, Dubrova YE. Single-molecule PCR analysis of germ line mutation induction by anticancer drugs in mice. Cancer Res. 2008 May 15;68(10):3630-6. PubMed PMID: 18483245.
6: Gasowska-Bajger B, Wojtasek H. Indirect oxidation of the antitumor agent procarbazine by tyrosinase--possible application in designing anti-melanoma prodrugs. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3296-300. Epub 2008 Apr 22. PubMed PMID: 18457951.
7: Armand JP, Ribrag V, Harrousseau JL, Abrey L. Reappraisal of the use of procarbazine in the treatment of lymphomas and brain tumors. Ther Clin Risk Manag. 2007 Jun;3(2):213-24. PubMed PMID: 18360630; PubMed Central PMCID: PMC1936303.
8: Grossman SA, Carson KA, Batchelor TT, Lesser G, Mikkelsen T, Alavi JB, Phuphanich S, Hammour T, Fisher JD, Supko JG. The effect of enzyme-inducing antiseizure drugs on the pharmacokinetics and tolerability of procarbazine hydrochloride. Clin Cancer Res. 2006 Sep 1;12(17):5174-81. PubMed PMID: 16951236.
9: Giordana MT, Ghimenti C, Leonardo E, Balteri I, Iudicello M, DuÃ² D. Molecular genetic study of a metastatic oligodendroglioma. J Neurooncol. 2004 Feb;66(3):265-71. PubMed PMID: 15015656.
10: Ewesuedo RB, Dolan ME. Pharmacokinetics of oral O6-benzylguanine and evidence of interaction with oral ketoconazole in the rat. Cancer Chemother Pharmacol. 2000;46(2):150-5. PubMed PMID: 10972485.