chlorambucil Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
588 305-03-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • chlorambucil
  • ambochlorin
  • amboclorin
  • chloraminophene
  • chlorbutin
  • chlorobutine
A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. 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)
  • Molecular weight: 304.21
  • Formula: C14H19Cl2NO2
  • CLOGP: 3.63
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 40.54
  • ALOGS: -3.59
  • ROTB: 9

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 12 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.66 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 82 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.26 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.80 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 18, 1957 FDA ASPEN GLOBAL INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neutropenia 147.05 44.62 45 485 21503 2336052
Febrile neutropenia 92.36 44.62 27 503 10855 2346700
Myelodysplastic syndrome 80.03 44.62 18 512 2542 2355013
Progressive multifocal leukoencephalopathy 71.56 44.62 16 514 2196 2355359
Thrombocytopenia 69.71 44.62 25 505 19106 2338449
Off label use 63.90 44.62 35 495 73563 2283992
Anaemia 61.68 44.62 27 503 34765 2322790

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pneumonia 286.75 57.55 121 904 46061 1699695
Neutropenia 197.50 57.55 72 953 18188 1727568
Acute myeloid leukaemia 141.95 57.55 37 988 3004 1742752
Febrile neutropenia 139.27 57.55 49 976 11051 1734705
Pyrexia 130.14 57.55 71 954 46329 1699427
T-cell lymphoma stage IV 96.07 57.55 13 1012 17 1745739
Thrombocytopenia 95.81 57.55 45 980 21204 1724552
Microsporidia infection 94.57 57.55 14 1011 47 1745709
Neutropenic sepsis 93.49 57.55 23 1002 1469 1744287
Cerebral aspergillosis 87.45 57.55 15 1010 150 1745606
Second primary malignancy 85.30 57.55 20 1005 1039 1744717
Progressive multifocal leukoencephalopathy 81.48 57.55 21 1004 1618 1744138
Chronic lymphocytic leukaemia 78.26 57.55 18 1007 858 1744898
Infusion related reaction 78.24 57.55 28 997 6565 1739191
Myelodysplastic syndrome 75.48 57.55 23 1002 3266 1742490
Tumour lysis syndrome 75.31 57.55 20 1005 1731 1744025
Myositis 72.23 57.55 19 1006 1584 1744172
Hodgkin's disease 64.11 57.55 15 1010 770 1744986
Pancytopenia 60.25 57.55 27 998 11330 1734426

Pharmacologic Action:

SourceCodeDescription
ATC L01AA02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ALKYLATING AGENTS
Nitrogen mustard analogues
FDA MoA N0000000236 Alkylating Activity
FDA EPC N0000175558 Alkylating Drug
MeSH PA D000477 Alkylating Agents
CHEBI has role CHEBI:88188 drug allergen
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35705 immunosuppressive agent
MeSH PA D000970 Antineoplastic Agents
MeSH PA D018906 Antineoplastic Agents, Alkylating
MeSH PA D009676 Noxae

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic lymphoid leukemia, disease indication 92814006
Hodgkin's disease indication 118599009
Follicular non-Hodgkin's lymphoma indication 308121000
Minimal change disease off-label use 44785005 DOID:10966
Mycosis fungoides off-label use 118618005
Waldenström macroglobulinemia off-label use 190818004 DOID:0050747
Primary cutaneous T-cell lymphoma off-label use 400122007
Lowered convulsive threshold contraindication 19260006
Lymphocytopenia contraindication 48813009 DOID:614
Fibrosis of lung contraindication 51615001 DOID:3770
Nephrotic syndrome contraindication 52254009 DOID:1184
Acute infectious disease contraindication 63171007
Interstitial pneumonia contraindication 64667001
Leukopenia contraindication 84828003 DOID:615
Acute leukemia, disease contraindication 91855006 DOID:12603
Secondary malignant neoplasm of bone marrow contraindication 94217008
Radiation oncology AND/OR radiotherapy contraindication 108290001
Seizure disorder contraindication 128613002
Drug-induced hepatitis contraindication 235876009
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.65 acidic
pKa2 3.71 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cathepsin D Enzyme IC50 8.93 WOMBAT-PK
Cathepsin E Enzyme IC50 8.78 WOMBAT-PK
Delta-type opioid receptor GPCR IC50 5.55 WOMBAT-PK
Disintegrin and metalloproteinase domain-containing protein 9 Enzyme IC50 7.25 WOMBAT-PK
DNA DNA ALKYLATING AGENT CHEMBL CHEMBL
Aldose reductase Enzyme IC50 5.03 DRUG MATRIX

External reference:

IDSource
D002699 MESH_DESCRIPTOR_UI
4018769 VUID
N0000147072 NUI
C0008163 UMLSCUI
D00266 KEGG_DRUG
18D0SL7309 UNII
603 INN_ID
46009007 SNOMEDCT_US
4018769 VANDF
71849 MMSL
002632 NDDF
2346 RXNORM
387249003 SNOMEDCT_US
4405 MMSL
d00188 MMSL
CHEBI:28830 CHEBI
CHEMBL515 ChEMBL_ID
DB00291 DRUGBANK_ID
CBL PDB_CHEM_ID
7143 IUPHAR_LIGAND_ID
2708 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
LEUKERAN HUMAN PRESCRIPTION DRUG LABEL 1 76388-635 TABLET, FILM COATED 2 mg ORAL NDA 14 sections