chlorambucil 🐶 Veterinary Use | 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
Progressive multifocal leukoencephalopathy 127.26 29.40 37 2052 11976 56278002
Neutropenia 95.59 29.40 64 2025 158103 56131875
Chronic lymphocytic leukaemia 89.34 29.40 21 2068 2967 56287011
Hypogammaglobulinaemia 68.92 29.40 20 2069 6406 56283572
Febrile neutropenia 54.85 29.40 39 2050 105506 56184472
Myelodysplastic syndrome 50.54 29.40 20 2069 16386 56273592
Campylobacter infection 46.90 29.40 10 2079 906 56289072
Encephalitis viral 46.29 29.40 11 2078 1624 56288354
Thrombocytopenia 46.02 29.40 39 2050 136185 56153793
B-cell small lymphocytic lymphoma 36.73 29.40 5 2084 27 56289951
Anaemia 34.78 29.40 46 2043 267465 56022513
Pyrexia 33.04 29.40 57 2032 418716 55871262
Diffuse large B-cell lymphoma 30.47 29.40 11 2078 7005 56282973
Lymphopenia 30.25 29.40 14 2075 16760 56273218

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
Acute myeloid leukaemia 192.59 24.92 79 4414 18593 31674258
Myositis 160.45 24.92 60 4433 11034 31681817
Microsporidia infection 150.44 24.92 31 4462 601 31692250
Progressive multifocal leukoencephalopathy 115.81 24.92 45 4448 9168 31683683
Second primary malignancy 101.50 24.92 38 4455 6994 31685857
Chronic lymphocytic leukaemia 99.68 24.92 34 4459 4782 31688069
Pneumonia 93.30 24.92 168 4325 335144 31357707
Myelodysplastic syndrome 84.06 24.92 45 4448 19206 31673645
Malignant transformation 82.71 24.92 20 4473 817 31692034
Neutropenia 80.45 24.92 99 4394 140265 31552586
Cerebral aspergillosis 72.53 24.92 20 4473 1378 31691473
Polymyositis 72.29 24.92 20 4473 1395 31691456
T-cell lymphoma stage IV 64.15 24.92 12 4481 137 31692714
Transformation to acute myeloid leukaemia 59.71 24.92 15 4478 718 31692133
Tumour lysis syndrome 58.94 24.92 33 4460 15352 31677499
Neutropenic sepsis 54.18 24.92 29 4464 12350 31680501
Chronic lymphocytic leukaemia recurrent 51.89 24.92 12 4481 403 31692448
Blood stem cell transplant failure 51.81 24.92 12 4481 406 31692445
Infusion related reaction 50.77 24.92 47 4446 48008 31644843
Thrombocytopenia 50.61 24.92 80 4413 142667 31550184
Hypogammaglobulinaemia 48.37 24.92 22 4471 6605 31686246
Enterococcal infection 45.50 24.92 23 4470 8708 31684143
Procalcitonin increased 43.35 24.92 14 4479 1659 31691192
Febrile neutropenia 40.02 24.92 66 4427 121783 31571068
Lymphopenia 39.85 24.92 25 4468 14304 31678547
Pyrexia 36.72 24.92 110 4383 303730 31389121
Malignant neoplasm progression 36.18 24.92 50 4443 78948 31613903
Chronic lymphocytic leukaemia refractory 35.40 24.92 7 4486 109 31692742
Respiratory tract infection 35.22 24.92 25 4468 17536 31675315
Pseudomonas infection 34.51 24.92 21 4472 11380 31681471
Treatment failure 33.90 24.92 35 4458 40757 31652094
Lymphadenopathy 30.41 24.92 27 4466 26094 31666757
Device related infection 29.93 24.92 22 4471 16277 31676574
Genotoxicity 28.80 24.92 5 4488 36 31692815
Peripheral T-cell lymphoma unspecified stage III 27.80 24.92 5 4488 45 31692806
Autoimmune haemolytic anaemia 27.78 24.92 13 4480 4159 31688692
Septic shock 27.50 24.92 40 4453 66118 31626733
Central nervous system lymphoma 27.47 24.92 9 4484 1115 31691736
Campylobacter infection 25.67 24.92 8 4485 845 31692006

FDA Adverse Event Reporting System (Geriatric)

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
Progressive multifocal leukoencephalopathy 213.50 24.39 74 5694 19140 70903536
Acute myeloid leukaemia 182.58 24.39 75 5693 30865 70891811
Myositis 166.25 24.39 60 5708 17429 70905247
Microsporidia infection 156.74 24.39 31 5737 867 70921809
Neutropenia 150.26 24.39 141 5627 257015 70665661
Chronic lymphocytic leukaemia 129.39 24.39 38 5730 5760 70916916
Myelodysplastic syndrome 119.41 24.39 55 5713 29730 70892946
Second primary malignancy 106.37 24.39 40 5728 13011 70909665
Hypogammaglobulinaemia 100.01 24.39 37 5731 11501 70911175
Pneumonia 90.51 24.39 168 5600 596064 70326612
Tumour lysis syndrome 87.33 24.39 40 5728 21320 70901356
Thrombocytopenia 82.12 24.39 99 5669 239011 70683665
Malignant transformation 81.72 24.39 19 5749 1154 70921522
Cerebral aspergillosis 79.02 24.39 20 5748 1736 70920940
T-cell lymphoma stage IV 70.25 24.39 12 5756 144 70922532
Polymyositis 68.40 24.39 20 5748 2981 70919695
Febrile neutropenia 67.51 24.39 83 5685 204235 70718441
Campylobacter infection 65.53 24.39 17 5751 1627 70921049
Lymphopenia 63.77 24.39 35 5733 27324 70895352
Malignant neoplasm progression 58.23 24.39 60 5708 121679 70800997
Pyrexia 56.04 24.39 140 5628 606812 70315864
Neutropenic sepsis 55.76 24.39 31 5737 24799 70897877
Chronic lymphocytic leukaemia recurrent 53.83 24.39 12 5756 603 70922073
Procalcitonin increased 49.07 24.39 15 5753 2601 70920075
Enterococcal infection 46.42 24.39 23 5745 14559 70908117
Respiratory tract infection 42.81 24.39 32 5736 42366 70880310
Diffuse large B-cell lymphoma 42.40 24.39 21 5747 13281 70909395
Infusion related reaction 40.73 24.39 64 5704 197470 70725206
Blood stem cell transplant failure 39.04 24.39 9 5759 526 70922150
Transformation to acute myeloid leukaemia 38.73 24.39 10 5758 939 70921737
Chronic lymphocytic leukaemia refractory 37.58 24.39 7 5761 141 70922535
Cytopenia 37.18 24.39 21 5747 17302 70905374
JC virus infection 36.80 24.39 13 5755 3538 70919138
Pseudomonas infection 35.38 24.39 21 5747 18973 70903703
Anaemia 33.92 24.39 90 5678 403333 70519343
Septic shock 32.87 24.39 43 5725 112215 70810461
Chills 31.34 24.39 48 5720 144738 70777938
Disease progression 31.22 24.39 50 5718 156622 70766054
Lymphadenopathy 30.73 24.39 28 5740 48763 70873913
B-cell small lymphocytic lymphoma 30.32 24.39 6 5762 168 70922508
Peripheral T-cell lymphoma unspecified stage III 29.84 24.39 5 5763 53 70922623
Device related infection 29.64 24.39 23 5745 32162 70890514
Encephalitis viral 29.40 24.39 10 5758 2432 70920244
Off label use 27.40 24.39 126 5642 742934 70179742
Squamous cell carcinoma 26.82 24.39 16 5752 14588 70908088
Central nervous system lymphoma 26.19 24.39 9 5759 2256 70920420
Dermatitis exfoliative generalised 26.16 24.39 12 5756 6402 70916274
Prostatic abscess 25.62 24.39 6 5762 376 70922300
Blood pressure decreased 25.16 24.39 34 5734 91481 70831195

FDA Adverse Event Reporting System (Pediatric)

None

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
MeSH PA D000970 Antineoplastic Agents
MeSH PA D018906 Antineoplastic Agents, Alkylating
MeSH PA D009676 Noxae
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:35705 immunosuppressive agents
CHEBI has role CHEBI:50903 carcinogen
CHEBI has role CHEBI:88188 allergenic drug

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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
Delta-type opioid receptor GPCR IC50 5.55 WOMBAT-PK
Cathepsin D Enzyme IC50 8.93 WOMBAT-PK
Cathepsin E Enzyme IC50 8.78 WOMBAT-PK
Disintegrin and metalloproteinase domain-containing protein 9 Enzyme IC50 7.25 WOMBAT-PK
Aldose reductase Enzyme IC50 5.03 DRUG MATRIX

External reference:

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

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
LEUKERAN HUMAN PRESCRIPTION DRUG LABEL 1 69784-610 TABLET, FILM COATED 2 mg ORAL NDA 25 sections
LEUKERAN HUMAN PRESCRIPTION DRUG LABEL 1 76388-635 TABLET, FILM COATED 2 mg ORAL NDA 25 sections
LEUKERAN HUMAN PRESCRIPTION DRUG LABEL 1 76388-635 TABLET, FILM COATED 2 mg ORAL NDA 25 sections