| Identification |
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| Name | Chlorambucil |
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| Accession Number | DB00291 (APRD00115) |
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| Type | Small Molecule |
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| Groups | Approved |
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| Description | A nitrogen mustard alkylating agent used as antineoplastic agent for the treatment of various malignant and nonmalignant diseases. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed) |
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| Structure | |
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| Synonyms | | 4-(P-Bis(beta-chloroethyl)aminophenyl)butyric acid | | 4-(p-bis(β-chloroethyl)aminophenyl)butyric acid | | 4-[p-[bis(2-chloroethyl)amino]phenyl]butyric acid | | Ambochlorin | | CHLORAMBUCIL | | Chloraminophen | | gamma-[P-Di(2-chloroethyl)aminophenyl]butyric acid | | Leukeran | | N,N-Di-2-chloroethyl-gamma-P-aminophenylbutyric acid | | N,N-di-2-chloroethyl-γ-p-aminophenylbutyric acid | | Phenylbutyric Acid Nitrogen Mustard | | γ-[p-di(2-chloroethyl)aminophenyl]butyric acid |
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| External Identifiers | Not Available |
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| Approved Prescription Products | | Name | Dosage | Strength | Route | Labeller | Marketing Start | Marketing End | | | Leukeran | Tablet, film coated | 2 mg/1 | Oral | Aspen Global Inc. | 1985-02-13 | Not applicable | US | | Leukeran | Tablet | 2 mg | Oral | Aspen Pharma Trading Limited | 1957-12-31 | Not applicable | Canada |
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| Approved Generic Prescription Products | Not Available |
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| Approved Over the Counter Products | Not Available |
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| Unapproved/Other Products | Not Available |
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| International Brands | | Name | Company |
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| Celkeran | Celon | | Chloraminophène | Techni-Pharma |
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| Brand mixtures | Not Available |
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| Salts | Not Available |
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| Categories | |
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| UNII | 18D0SL7309 |
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| CAS number | 305-03-3 |
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| Weight | Average: 304.212
Monoisotopic: 303.079284271 |
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| Chemical Formula | C14H19Cl2NO2 |
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| InChI Key | JCKYGMPEJWAADB-UHFFFAOYSA-N |
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| InChI | 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) |
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| IUPAC Name | 4-{4-[bis(2-chloroethyl)amino]phenyl}butanoic acid |
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| SMILES | OC(=O)CCCC1=CC=C(C=C1)N(CCCl)CCCl |
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| Pharmacology |
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| Indication | For treatment of chronic lymphatic (lymphocytic) leukemia, childhood minimal-change nephrotic syndrome, and malignant lymphomas including lymphosarcoma, giant follicular lymphoma, Hodgkin's disease, non-Hodgkin's lymphomas, and Waldenström’s Macroglobulinemia. |
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| Structured Indications Learn More" title="About Structured Indications" id="structured-indication-info" href="javascript:void(0);"> | |
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| Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" href="javascript:void(0);"> | | Phase | Status | Purpose | Conditions | Count | | 1 | Completed | Treatment | Chronic Lymphocytic Leukaemia (CLL) / Indolent Non-Hodgkin's Lymphomas / Mantle Cell Lymphoma (MCL) | 1 | | 1 | Recruiting | Treatment | Chronic Lymphocytic Leukaemia (CLL) | 1 | | 1, 2 | Completed | Not Available | Chronic Lymphocytic Leukaemia (CLL) | 1 | | 1, 2 | Terminated | Treatment | Chronic Lymphocytic Leukaemia (CLL) | 1 | | 2 | Active Not Recruiting | Treatment | Lymphoma NOS | 1 | | 2 | Active Not Recruiting | Treatment | Lymphoma, Mantle-Cell / Mantle Cell Lymphoma (MCL) | 1 | | 2 | Completed | Treatment | Chronic Lymphocytic Leukaemia (CLL) | 1 | | 2 | Completed | Treatment | Leukaemia, Lymphoblastic | 1 | | 2 | Completed | Treatment | Leukemia, Lymphocytic, Chronic | 1 | | 2 | Completed | Treatment | Lymphocytic Leukemia, Chronic | 1 | | 2 | Completed | Treatment | Mantle Cell Lymphoma (MCL) | 1 | | 2 | Recruiting | Treatment | MALT Lymphoma | 1 | | 2 | Terminated | Treatment | Chronic Lymphocytic Leukaemia (CLL) | 1 | | 3 | Active Not Recruiting | Treatment | B-Cell Chronic Lymphocytic Leukemia (B-CLL) | 1 | | 3 | Active Not Recruiting | Treatment | Chronic Lymphocytic Leukaemia (CLL) | 1 | | 3 | Active Not Recruiting | Treatment | Chronic Lymphocytic Leukaemia (CLL) / Lymphoma, Small-Cell | 1 | | 3 | Active Not Recruiting | Treatment | Gastric Cancers | 1 | | 3 | Active Not Recruiting | Treatment | Leukemia, Lymphocytic, Chronic | 1 | | 3 | Active Not Recruiting | Treatment | Leukemias | 2 | | 3 | Active Not Recruiting | Treatment | Lymphocytic Leukemia, Chronic | 3 | | 3 | Active Not Recruiting | Treatment | Lymphoma NOS | 3 | | 3 | Active Not Recruiting | Treatment | Lymphoma, Mucosa-Associated Lymphoid Tissue | 1 | | 3 | Completed | Treatment | Chronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL) | 1 | | 3 | Completed | Treatment | Glomerulonephritis, Membranous / Glomerulosclerosis, Focal | 1 | | 3 | Completed | Treatment | Leukemias | 1 | | 3 | Completed | Treatment | Lymphoma NOS | 2 | | 3 | Completed | Treatment | Lymphoplasmacytic Lymphoma / Splenic Marginal Zone Lymphoma / Waldenstrom's Macroglobulinemia (WM) | 1 | | 3 | Recruiting | Treatment | Chronic Lymphocytic Leukaemia (CLL) | 3 | | 3 | Recruiting | Treatment | Chronic Lymphocytic Leukaemia (CLL) / Leukemias / Neoplasms | 1 | | 3 | Recruiting | Treatment | Lymphocytic Leukemia, Chronic | 1 | | 4 | Active Not Recruiting | Treatment | Lymphocytic Leukemia, Chronic | 1 | | 4 | Approved for Marketing | Not Available | Chronic Lymphocytic Leukaemia (CLL) | 1 | | 4 | Completed | Treatment | Lymphocytic Leukemia, Chronic | 1 | | 4 | Completed | Treatment | Uveitis | 1 | | Not Available | Active Not Recruiting | Treatment | Lymphoma NOS | 2 |
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| Pharmacodynamics | Chlorambucil is an antineoplastic in the class of alkylating agents that 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. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. |
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| Mechanism of action | Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.| Target | Kind | Pharmacological action | Actions | Organism | UniProt ID | |
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| DNA | Nucleotide | unknown | cross-linking/alkylation | Human | not applicable | details |
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| Related Articles | |
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| Absorption | Not Available |
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| Volume of distribution | Not Available |
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| Protein binding | 99% |
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| Metabolism | Not Available |
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| Route of elimination | Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard. The pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary excretion. |
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| Half life | 1.5 hours |
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| Clearance | Not Available |
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| Toxicity | Not Available |
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| Affected organisms | |
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| Pathways | Not Available |
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| SNP Mediated Effects | Not Available |
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| SNP Mediated Adverse Drug Reactions | Not Available |
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| Interactions |
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| Drug Interactions | | Drug | Interaction | Drug group |
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| Acetyldigitoxin | Acetyldigitoxin may decrease the cardiotoxic activities of Chlorambucil. | Approved | | ALT-110 | The risk or severity of adverse effects can be increased when Chlorambucil is combined with ALT-110. | Investigational | | Anvirzel | Anvirzel may decrease the cardiotoxic activities of Chlorambucil. | Investigational | | BCG | The therapeutic efficacy of Bcg can be decreased when used in combination with Chlorambucil. | Investigational | | Bevacizumab | Bevacizumab may increase the cardiotoxic activities of Chlorambucil. | Approved, Investigational | | Cabazitaxel | The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Chlorambucil. | Approved | | CDX-110 | The risk or severity of adverse effects can be increased when Chlorambucil is combined with CDX-110. | Investigational | | Clozapine | The risk or severity of adverse effects can be increased when Chlorambucil is combined with Clozapine. | Approved | | Cyclophosphamide | Cyclophosphamide may increase the cardiotoxic activities of Chlorambucil. | Approved, Investigational | | Denosumab | The risk or severity of adverse effects can be increased when Denosumab is combined with Chlorambucil. | Approved | | Deslanoside | Deslanoside may decrease the cardiotoxic activities of Chlorambucil. | Approved | | Digitoxin | Digitoxin may decrease the cardiotoxic activities of Chlorambucil. | Approved | | Digoxin | Digoxin may decrease the cardiotoxic activities of Chlorambucil. | Approved | | Docetaxel | The risk or severity of adverse effects can be increased when Docetaxel is combined with Chlorambucil. | Approved, Investigational | | Fingolimod | Chlorambucil may increase the immunosuppressive activities of Fingolimod. | Approved, Investigational | | G17DT | The risk or severity of adverse effects can be increased when Chlorambucil is combined with G17DT. | Investigational | | GI-5005 | The risk or severity of adverse effects can be increased when Chlorambucil is combined with GI-5005. | Investigational | | INGN 201 | The risk or severity of adverse effects can be increased when Chlorambucil is combined with INGN 201. | Investigational | | INGN 225 | The risk or severity of adverse effects can be increased when Chlorambucil is combined with INGN 225. | Investigational | | Leflunomide | The risk or severity of adverse effects can be increased when Chlorambucil is combined with Leflunomide. | Approved, Investigational | | Metamizole | The risk or severity of adverse effects can be increased when Metamizole is combined with Chlorambucil. | Withdrawn | | Natalizumab | The risk or severity of adverse effects can be increased when Chlorambucil is combined with Natalizumab. | Approved, Investigational | | Ouabain | Ouabain may decrease the cardiotoxic activities of Chlorambucil. | Approved | | Paclitaxel | The risk or severity of adverse effects can be increased when Paclitaxel is combined with Chlorambucil. | Approved, Vet Approved | | Pimecrolimus | The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Chlorambucil. | Approved, Investigational | | Rabies vaccine | The risk or severity of adverse effects can be increased when Chlorambucil is combined with Rabies vaccine. | Approved | | Rabies vaccine | The therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Chlorambucil. | Approved | | Roflumilast | Roflumilast may increase the immunosuppressive activities of Chlorambucil. | Approved | | Sipuleucel-T | The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Chlorambucil. | Approved | | SRP 299 | The risk or severity of adverse effects can be increased when Chlorambucil is combined with SRP 299. | Investigational | | Tacrolimus | The risk or severity of adverse effects can be increased when Tacrolimus is combined with Chlorambucil. | Approved, Investigational | | TG4010 | The risk or severity of adverse effects can be increased when Chlorambucil is combined with TG4010. | Investigational | | Tofacitinib | Chlorambucil may increase the immunosuppressive activities of Tofacitinib. | Approved, Investigational | | Trastuzumab | Trastuzumab may increase the cardiotoxic activities of Chlorambucil. | Approved, Investigational |
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| Food Interactions | - Drink liberally.
- Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.
- Food reduces bioavailability.
- Take on an empty stomach.
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| References |
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| Synthesis Reference | Phillips, A. P. and Mentha, J.W.; U.S.Patent 3,046,301; July 24, 1962; assigned to Burroughs
Wellcome & Co. (U.S.A.) Inc. US2944079 |
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| General References | - Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [PubMed:11114313 ]
- Yang K, Tan J, Wu T: Alkylating agents for Waldenstrom's macroglobulinaemia. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006719. doi: 10.1002/14651858.CD006719.pub3. [PubMed:19160296 ]
- Foon KA, Hallek MJ: Changing paradigms in the treatment of chronic lymphocytic leukemia. Leukemia. 2010 Mar;24(3):500-11. doi: 10.1038/leu.2009.266. Epub 2009 Dec 24. [PubMed:20033051 ]
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| External Links | |
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| ATC Codes | L01AA02 |
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| AHFS Codes | |
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| PDB Entries | Not Available |
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| FDA label | Not Available |
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| MSDS | Download (74.6 KB) |
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| ADMET |
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| Predicted ADMET features | | Property | Value | Probability |
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| Human Intestinal Absorption | + | 0.9739 | | Blood Brain Barrier | + | 0.7889 | | Caco-2 permeable | + | 0.5734 | | P-glycoprotein substrate | Non-substrate | 0.6721 | | P-glycoprotein inhibitor I | Non-inhibitor | 0.9394 | | P-glycoprotein inhibitor II | Non-inhibitor | 0.9222 | | Renal organic cation transporter | Non-inhibitor | 0.6185 | | CYP450 2C9 substrate | Non-substrate | 0.7651 | | CYP450 2D6 substrate | Non-substrate | 0.744 | | CYP450 3A4 substrate | Non-substrate | 0.6044 | | CYP450 1A2 substrate | Non-inhibitor | 0.9045 | | CYP450 2C9 inhibitor | Non-inhibitor | 0.9071 | | CYP450 2D6 inhibitor | Non-inhibitor | 0.9231 | | CYP450 2C19 inhibitor | Non-inhibitor | 0.909 | | CYP450 3A4 inhibitor | Non-inhibitor | 0.8309 | | CYP450 inhibitory promiscuity | Low CYP Inhibitory Promiscuity | 0.9576 | | Ames test | AMES toxic | 0.9107 | | Carcinogenicity | Non-carcinogens | 0.7851 | | Biodegradation | Not ready biodegradable | 0.9378 | | Rat acute toxicity | 3.5709 LD50, mol/kg | Not applicable | | hERG inhibition (predictor I) | Weak inhibitor | 0.6531 | | hERG inhibition (predictor II) | Non-inhibitor | 0.8609 |
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. ( 23092397 ) |
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| Pharmacoeconomics |
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| Manufacturers | - Smithkline beecham corp dba glaxosmithkline
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| Packagers | |
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| Dosage forms | | Form | Route | Strength |
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| Tablet | Oral | 2 mg | | Tablet, film coated | Oral | 2 mg/1 |
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| Prices | | Unit description | Cost | Unit |
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| Leukeran 2 mg tablet | 3.92USD | tablet |
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only. |
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| Patents | Not Available |
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| Properties |
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| State | Solid |
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| Experimental Properties | | Property | Value | Source |
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| melting point | 65 °C | PhysProp | | water solubility | 1.24E+004 mg/L | Not Available | | logP | 1.70 | HANSCH,C ET AL. (1995), pH 7.4 | | pKa | 5.75 | HANSCH,C & LEO,AJ (1987) |
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| Predicted Properties | |
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| Spectra |
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| Mass Spec (NIST) | Download (8.25 KB) |
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| Spectra | |
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| Taxonomy |
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| Description | This compound belongs to the class of organic compounds known as nitrogen mustard compounds. These are compounds having two beta-haloalkyl groups bound to a nitrogen atom. |
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| Kingdom | Organic compounds |
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| Super Class | Organonitrogen compounds |
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| Class | Nitrogen mustard compounds |
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| Sub Class | Not Available |
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| Direct Parent | Nitrogen mustard compounds |
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| Alternative Parents | |
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| Substituents | - Substituted aniline
- Dialkylarylamine
- Nitrogen mustard
- Aniline
- Benzenoid
- Monocyclic benzene moiety
- Tertiary amine
- Monocarboxylic acid or derivatives
- Carboxylic acid
- Carboxylic acid derivative
- Hydrocarbon derivative
- Organooxygen compound
- Organochloride
- Organohalogen compound
- Carbonyl group
- Amine
- Alkyl halide
- Alkyl chloride
- Aromatic homomonocyclic compound
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| Molecular Framework | Aromatic homomonocyclic compounds |
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| External Descriptors | |
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