WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100150
CAS#: 305-03-3
Description: Chlorambucil is an orally-active antineoplastic aromatic nitrogen mustard. Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis.
MedKoo Cat#: 100150
Name: Chlorambucil
CAS#: 305-03-3
Chemical Formula: C14H19Cl2NO2
Exact Mass: 303.07928
Molecular Weight: 304.21
Elemental Analysis: C, 55.27; H, 6.30; Cl, 23.31; N, 4.60; O, 10.52
Synonym: chlorambucilum; chloraminophen; Chlorbutin; chlorbutine; chlorbutinum; chloroambucil; chlorobutin; chlorobutine; Leukersan; Leukoran; Lympholysin; phenylbutyric acid nitrogen mustard; US brand names: Ambochlorin; Amboclorin; Leukeran; Linfolizin. Foreign brand names: Altichlorambucil; Chloraminophene; Linfolysin. Abbreviations: CHL CLB; Code names: CB1348; WR139013.
IUPAC/Chemical Name: 4-(4-(bis(2-chloroethyl)amino)phenyl)butanoic acid
InChi Key: JCKYGMPEJWAADB-UHFFFAOYSA-N
InChi Code: InChI=1S/C14H19Cl2NO2/c15-8-10-17(11-9-16)13-6-4-12(5-7-13)2-1-3-14(18)19/h4-7H,1-3,8-11H2,(H,18,19)
SMILES Code: O=C(O)CCCC1=CC=C(N(CCCl)CCCl)C=C1
Appearance: Pale brown to brown 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
The following data is based on the product molecular weight 304.21 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 |
1: Rehman SU, Sarwar T, Ishqi HM, Husain MA, Hasan Z, Tabish M. Deciphering the interactions between chlorambucil and calf thymus DNA: A multi-spectroscopic and molecular docking study. Arch Biochem Biophys. 2015 Jan 15;566:7-14. doi: 10.1016/j.abb.2014.12.013. Epub 2014 Dec 17. PubMed PMID: 25528167.
2: Soler M, González-Bártulos M, Figueras E, Ribas X, Costas M, Massaguer A, Planas M, Feliu L. Enzyme-triggered delivery of chlorambucil from conjugates based on the cell-penetrating peptide BP16. Org Biomol Chem. 2015 Jan 21;13(5):1470-80. doi: 10.1039/c4ob01875c. PubMed PMID: 25474438.
3: Nazarov AA, Meier SM, Zava O, Nosova YN, Milaeva ER, Hartinger CG, Dyson PJ. Protein ruthenation and DNA alkylation: chlorambucil-functionalized RAPTA complexes and their anticancer activity. Dalton Trans. 2014 Nov 13. [Epub ahead of print] PubMed PMID: 25407500.
4: Wang X, Li J, Xu C, Li Y, Gong T, Sun X, Fu Y, He Q, Zhang Z. Scopine as a novel brain-targeting moiety enhances the brain uptake of chlorambucil. Bioconjug Chem. 2014 Nov 19;25(11):2046-54. doi: 10.1021/bc5004108. Epub 2014 Nov 6. PubMed PMID: 25350514.
5: Olayinka ET, Ore A. Kolaviron and L-ascorbic Acid attenuate chlorambucil-induced testicular oxidative stress in rats. J Toxicol. 2014;2014:587015. doi: 10.1155/2014/587015. Epub 2014 Sep 17. PubMed PMID: 25309592; PubMed Central PMCID: PMC4182070.
6: Goede V, Eichhorst B, Fischer K, Wendtner CM, Hallek M. Past, present and future role of chlorambucil in the treatment of chronic lymphocytic leukemia. Leuk Lymphoma. 2014 Nov 20:1-8. [Epub ahead of print] PubMed PMID: 25219593.
7: López-Lluva MT, de la Nieta-GarcÃa MD, Piqueras-Flores J, Arambarri-Segura M, MartÃnez-Calero A, Rivera-Hernández F. Chlorambucil-induced cytomegalovirus infection: a case report. J Med Case Rep. 2014 Aug 20;8:280. doi: 10.1186/1752-1947-8-280. PubMed PMID: 25142684; PubMed Central PMCID: PMC4164317.
8: Asamitsu S, Kawamoto Y, Hashiya F, Hashiya K, Yamamoto M, Kizaki S, Bando T, Sugiyama H. Sequence-specific DNA alkylation and transcriptional inhibition by long-chain hairpin pyrrole-imidazole polyamide-chlorambucil conjugates targeting CAG/CTG trinucleotide repeats. Bioorg Med Chem. 2014 Sep 1;22(17):4646-57. doi: 10.1016/j.bmc.2014.07.019. Epub 2014 Jul 22. PubMed PMID: 25127467.
9: Wang X, Zhang Q, Lin Q, Zhang Y, Zhang ZR. Validated LC-MS/MS method for the simultaneous determination of chlorambucil and its prodrug in mouse plasma and brain, and application to pharmacokinetics. J Pharm Biomed Anal. 2014 Oct;99:74-8. doi: 10.1016/j.jpba.2014.07.010. Epub 2014 Jul 17. PubMed PMID: 25090578.
10: Martinelli G, Montoro J, Vanazzi A, Andreola G, Liptrott S, Radice D, Negri M, Preda L, Pruneri G, Laszlo D. Chlorambucil-rituximab as first-line therapy in patients affected by follicular non-Hodgkin's lymphoma: a retrospective single-centre study. Hematol Oncol. 2014 Jul 22. doi: 10.1002/hon.2154. [Epub ahead of print] PubMed PMID: 25047267.
Chlorambucil (marketed as Leukeran by GlaxoSmithKline) is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia. It is a nitrogen mustard alkylating agent and can be given orally. In the past, chlorambucil has been used for treating some types of non-Hodgkin lymphoma, Waldenström macroglobulinemia, polycythemia vera, trophoblastic neoplasms, and ovarian carcinoma. It also has been used as an immunosuppressive drug for various autoimmune and inflammatory conditions, such as nephrotic syndrome. Its current use is mainly in chronic lymphocytic leukemia, as it is well tolerated by most patients, though chlorambucil has been largely replaced by fludarabine as first-line treatment in younger patients. see http://en.wikipedia.org/wiki/Chlorambucil.
LEUKERAN (chlorambucil) was first synthesized by Everett et al. It is a bifunctional alkylating agent of the nitrogen mustard type that has been found active against selected human neoplastic diseases. Chlorambucil is known chemically as 4-[bis(2-chlorethyl)amino]benzenebutanoic acid. Chlorambucil hydrolyzes in water and has a pKa of 5.8. LEUKERAN (chlorambucil) is available in tablet form for oral administration. Each film-coated tablet contains 2 mg chlorambucil and the inactive ingredients colloidal silicon dioxide, hypromellose, lactose (anhydrous), macrogol/PEG 400, microcrystalline cellulose, red iron oxide, stearic acid, titanium dioxide, and yellow iron oxide.
CLINICAL PHARMACOLOGY
Chlorambucil is rapidly and completely absorbed from the gastrointestinal tract. After single oral doses of 0.6 to 1.2 mg/kg, peak plasma chlorambucil levels (Cmax) are reached within 1 hour and the terminal elimination half-life (tœ) of the parent drug is estimated at 1.5 hours. Chlorambucil undergoes rapid metabolism to phenylacetic acid mustard, the major metabolite, and the combined chlorambucil and phenylacetic acid mustard urinary excretion is extremely low — less than 1% in 24 hours. In a study of 12 patients given single oral doses of 0.2 mg/kg of LEUKERAN, the mean dose (12 mg) adjusted (± SD) plasma chlorambucil Cmax was 492 ± 160 ng/mL, the AUC was 883 ± 329 ng•h/mL, tœ was 1.3 ± 0.5 hours, and the W was 0.83 ± 0.53 hours. For the major metabolite, phenylacetic acid mustard, the mean dose (12 mg) adjusted (± SD) plasma Cmax was 306 ± 73 ng/mL, the AUC was 1204 ± 285 ng•h/mL, the t/ was 1.8 ± 0.4 hours, and the tmax was 1.9 ± 0.7 hours. Chlorambucil and its metabolites are extensively bound to plasma and tissue proteins. In vitro, chlorambucil is 99% bound to plasma proteins, specifically albumin. Cerebrospinal fluid levels of chlorambucil have not been determined. Evidence of human teratogenicity suggests that the drug crosses the placenta. Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard, which has antineoplastic activity. Chlorambucil and its major metabolite spontaneously degrade in vivo forming monohydroxy and dihydroxy derivatives. After a single dose of radiolabeled chlorambucil (14C), approximately 15% to 60% of the radioactivity appears in the urine after 24 hours. Again, less than 1% of the urinary radioactivity is in the form of chlorambucil or phenylacetic acid mustard. In summary, the pharmacokinetic data suggest that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary excretion.
