Chlorambucil (T3D4684)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-09-11 02:04:51 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4684
Identification
Common NameChlorambucil
ClassSmall Molecule
DescriptionA 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).
Compound Type
  • Amine
  • Antineoplastic Agent, Alkylating
  • Drug
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
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
Celkeran
Chlocambucil
CHLORAMBUCIL
Chloraminophen
Chloraminophene
Chlorbutin
Chlorbutine
Chloroambucil
Chlorobutin
Chlorobutine
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
Chemical FormulaC14H19Cl2NO2
Average Molecular Mass304.212 g/mol
Monoisotopic Mass303.079 g/mol
CAS Registry Number305-03-3
IUPAC Name4-{4-[bis(2-chloroethyl)amino]phenyl}butanoic acid
Traditional Namechlorambucil
SMILESOC(=O)CCCC1=CC=C(C=C1)N(CCCl)CCCl
InChI IdentifierInChI=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)
InChI KeyInChIKey=JCKYGMPEJWAADB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as nitrogen mustard compounds. Nitrogen mustard compounds are compounds having two beta-haloalkyl groups bound to a nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassNitrogen mustard compounds
Direct ParentNitrogen mustard compounds
Alternative Parents
Substituents
  • Aniline or substituted anilines
  • Dialkylarylamine
  • Tertiary aliphatic/aromatic amine
  • Nitrogen mustard
  • Monocyclic benzene moiety
  • Benzenoid
  • Amino acid or derivatives
  • Amino acid
  • Tertiary amine
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Alkyl chloride
  • Organohalogen compound
  • Organochloride
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Alkyl halide
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point65°C
Boiling PointNot Available
Solubility1.24E+004 mg/L
LogP1.7
Predicted Properties
PropertyValueSource
Water Solubility0.077 g/LALOGPS
logP3.81ALOGPS
logP3.94ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)4.46ChemAxon
pKa (Strongest Basic)1.72ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity79.68 m³·mol⁻¹ChemAxon
Polarizability31.98 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-066u-2790000000-bf4786edba412b2ccaae2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-024i-5393000000-3be6fe379684458bfa852017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-004i-0002900000-472e293a011d716bb5a82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0zfr-0519000000-1bca00472dfc8c30a4652017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udr-0096000000-3899963778fe2e6e88de2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-08g0-3591000000-6ae3349b3f490c58310d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0j4i-6920000000-15483700b73ee5d5c44b2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0039000000-b8ff9ca35aa22b00bd352016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0uxr-1193000000-7606e0823853c0c258ee2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9540000000-f5720e555315984712a62016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-9004000000-788a1a6f740556f914412021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9000000000-724cdb1db65352c21f6c2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9100000000-58ace4115f9b048a722e2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udr-0098000000-d1dce37c9e184d7829de2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kr-0091000000-f4d0cc5c505d1414f7cd2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014m-1920000000-59f8073bfe41e45f2bdb2021-09-24View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0udi-2491000000-ddb7d5da8316562dba362014-09-20View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityAlkylating 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.
MetabolismRoute 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. Half Life: 1.5 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)1, carcinogenic to humans. (3)
Uses/SourcesFor 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 Waldenstrн_mду»s Macroglobulinemia.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00291
HMDB IDHMDB14436
PubChem Compound ID2708
ChEMBL IDCHEMBL515
ChemSpider ID2607
KEGG IDC06900
UniProt IDNot Available
OMIM ID
ChEBI ID28830
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDCBL
ACToR IDNot Available
Wikipedia LinkChlorambucil
References
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.

MSDSLink
General References
  1. 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. [11114313 ]
  2. 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. [19160296 ]
  3. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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. [17016423 ]
  3. Begleiter A, Mowat M, Israels LG, Johnston JB: Chlorambucil in chronic lymphocytic leukemia: mechanism of action. Leuk Lymphoma. 1996 Oct;23(3-4):187-201. [9031099 ]
  4. Kashiwazaki G, Bando T, Shinohara K, Minoshima M, Kumamoto H, Nishijima S, Sugiyama H: Alkylation of a human telomere sequence by heterotrimeric chlorambucil PI polyamide conjugates. Bioorg Med Chem. 2010 Apr 15;18(8):2887-93. doi: 10.1016/j.bmc.2010.03.011. Epub 2010 Mar 10. [20350810 ]
  5. Bielawska A, Bielawski K, Muszynska A: Synthesis and biological evaluation of new cyclic amidine analogs of chlorambucil. Farmaco. 2004 Feb;59(2):111-7. [14871502 ]
  6. Minoshima M, Bando T, Shinohara K, Sugiyama H: Molecular design of sequence specific DNA alkylating agents. Nucleic Acids Symp Ser (Oxf). 2009;(53):69-70. doi: 10.1093/nass/nrp035. [19749264 ]