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) 0.09 mg/mL Bocci G, Oprea TI, Benet LZ
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 126.56 27.08 37 2186 12934 63473865
Neutropenia 97.82 27.08 66 2157 174939 63311860
Hypogammaglobulinaemia 81.32 27.08 23 2200 7132 63479667
Campylobacter infection 63.04 27.08 13 2210 1063 63485736
Febrile neutropenia 52.83 27.08 39 2184 118410 63368389
Thrombocytopenia 52.70 27.08 43 2180 151114 63335685
Myelodysplastic syndrome 51.25 27.08 20 2203 16734 63470065
Neutropenic infection 48.89 27.08 11 2212 1356 63485443
Disease progression 47.19 27.08 37 2186 122721 63364078
Encephalitis viral 46.30 27.08 11 2212 1721 63485078
Chronic lymphocytic leukaemia 41.80 27.08 11 2212 2603 63484196
Anaemia 33.52 27.08 46 2177 293384 63193415
Chronic lymphocytic leukaemia recurrent 33.34 27.08 6 2217 238 63486561
Off label use 32.41 27.08 72 2151 674390 62812409
Pyrexia 31.87 27.08 58 2165 470420 63016379
Blood disorder 31.47 27.08 11 2212 6760 63480039
Lymphopenia 29.84 27.08 14 2209 18313 63468486
Tumour lysis syndrome 28.43 27.08 11 2212 8979 63477820
Diffuse large B-cell lymphoma 27.76 27.08 10 2213 6702 63480097

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 207.55 24.15 81 4486 18189 34934175
Myositis 167.62 24.15 62 4505 12008 34940356
Microsporidia infection 149.54 24.15 31 4536 675 34951689
Progressive multifocal leukoencephalopathy 116.83 24.15 45 4522 9719 34942645
Second primary malignancy 103.90 24.15 39 4528 7847 34944517
Pneumonia 94.96 24.15 169 4398 362458 34589906
Myelodysplastic syndrome 87.61 24.15 45 4522 19163 34933201
Malignant transformation 84.00 24.15 20 4547 831 34951533
Neutropenia 79.74 24.15 100 4467 156678 34795686
Cerebral aspergillosis 73.67 24.15 20 4547 1412 34950952
Polymyositis 73.38 24.15 20 4547 1433 34950931
T-cell lymphoma stage IV 65.53 24.15 12 4555 132 34952232
Tumour lysis syndrome 60.99 24.15 34 4533 17025 34935339
Transformation to acute myeloid leukaemia 60.12 24.15 15 4552 759 34951605
Neutropenic sepsis 53.51 24.15 29 4538 13738 34938626
Chronic lymphocytic leukaemia recurrent 53.01 24.15 12 4555 398 34951966
Blood stem cell transplant failure 52.67 24.15 12 4555 410 34951954
Thrombocytopenia 51.46 24.15 81 4486 156166 34796198
Infusion related reaction 50.07 24.15 47 4520 53010 34899354
Hypogammaglobulinaemia 46.82 24.15 22 4545 7718 34944646
Enterococcal infection 45.89 24.15 23 4544 9283 34943081
Procalcitonin increased 43.85 24.15 14 4553 1737 34950627
Febrile neutropenia 39.66 24.15 67 4500 136782 34815582
Lymphopenia 38.71 24.15 25 4542 16310 34936054
Malignant neoplasm progression 38.13 24.15 52 4515 87994 34864370
Chronic lymphocytic leukaemia refractory 37.51 24.15 7 4560 86 34952278
Pyrexia 36.03 24.15 110 4457 332903 34619461
Bone marrow failure 35.71 24.15 30 4537 29223 34923141
Pseudomonas infection 34.49 24.15 21 4546 12361 34940003
Respiratory tract infection 34.45 24.15 25 4542 19687 34932677
Treatment failure 32.34 24.15 35 4532 46662 34905702
Device related infection 30.44 24.15 22 4545 17215 34935149
Genotoxicity 29.20 24.15 5 4562 36 34952328
Central nervous system lymphoma 28.99 24.15 9 4558 1019 34951345
Autoimmune haemolytic anaemia 27.87 24.15 13 4554 4483 34947881
Septic shock 27.48 24.15 40 4527 71794 34880570
Lymphadenopathy 26.41 24.15 25 4542 28438 34923926
Disease progression 26.22 24.15 49 4518 108028 34844336
Campylobacter infection 25.64 24.15 8 4559 921 34951443
Diffuse large B-cell lymphoma 24.46 24.15 14 4553 7356 34945008

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 214.28 23.62 74 5908 20526 79717880
Acute myeloid leukaemia 202.62 23.62 79 5903 30806 79707600
Myositis 173.11 23.62 62 5920 19106 79719300
Microsporidia infection 156.97 23.62 31 5951 935 79737471
Neutropenia 152.15 23.62 144 5838 287566 79450840
Myelodysplastic syndrome 122.75 23.62 55 5927 30246 79708160
Hypogammaglobulinaemia 109.81 23.62 40 5942 12911 79725495
Second primary malignancy 109.45 23.62 41 5941 14309 79724097
Tumour lysis syndrome 89.18 23.62 41 5941 23898 79714508
Pneumonia 89.16 23.62 169 5813 660077 79078329
Thrombocytopenia 85.17 23.62 102 5880 265157 79473249
Malignant transformation 82.53 23.62 19 5963 1199 79737207
Cerebral aspergillosis 80.17 23.62 20 5962 1776 79736630
Campylobacter infection 79.45 23.62 20 5962 1843 79736563
T-cell lymphoma stage IV 71.45 23.62 12 5970 141 79738265
Polymyositis 69.77 23.62 20 5962 3016 79735390
Febrile neutropenia 66.29 23.62 84 5898 230915 79507491
Chronic lymphocytic leukaemia recurrent 65.35 23.62 14 5968 634 79737772
Lymphopenia 62.79 23.62 35 5947 30522 79707884
Malignant neoplasm progression 60.31 23.62 62 5920 135928 79602478
Disease progression 57.61 23.62 70 5912 184292 79554114
Neutropenic sepsis 55.60 23.62 31 5951 27033 79711373
Pyrexia 54.23 23.62 141 5841 678568 79059838
Procalcitonin increased 48.21 23.62 15 5967 2991 79735415
Enterococcal infection 46.63 23.62 23 5959 15637 79722769
Diffuse large B-cell lymphoma 42.71 23.62 20 5962 12129 79726277
Neutropenic infection 42.69 23.62 13 5969 2414 79735992
Respiratory tract infection 41.17 23.62 32 5950 48657 79689749
Cytopenia 40.92 23.62 23 5959 20360 79718046
Blood stem cell transplant failure 39.76 23.62 9 5973 526 79737880
Chronic lymphocytic leukaemia refractory 39.27 23.62 7 5975 119 79738287
Transformation to acute myeloid leukaemia 39.04 23.62 10 5972 987 79737419
Chronic lymphocytic leukaemia 37.44 23.62 14 5968 4852 79733554
Infusion related reaction 37.29 23.62 64 5918 230173 79508233
JC virus infection 36.69 23.62 13 5969 3868 79734538
Pseudomonas infection 35.09 23.62 21 5961 20882 79717524
Septic shock 34.12 23.62 44 5938 122757 79615649
Bone marrow failure 33.57 23.62 29 5953 51078 79687328
Anaemia 32.91 23.62 90 5892 444925 79293481
Off label use 31.71 23.62 143 5839 907072 78831334
Chills 30.59 23.62 48 5934 160186 79578220
Device related infection 29.99 23.62 23 5959 34271 79704135
Squamous cell carcinoma 29.66 23.62 17 5965 15605 79722801
Encephalitis viral 29.65 23.62 10 5972 2569 79735837
Blood disorder 27.18 23.62 13 5969 8260 79730146
Central nervous system lymphoma 26.81 23.62 9 5973 2280 79736126
Lymphadenopathy 26.74 23.62 26 5956 53221 79685185
Prostatic abscess 25.70 23.62 6 5976 402 79738004
Dermatitis exfoliative generalised 25.70 23.62 12 5970 7229 79731177
Blood pressure decreased 25.09 23.62 34 5948 99432 79638974
Panniculitis 24.94 23.62 14 5968 12357 79726049
Pain 24.69 23.62 11 5971 703791 79034615
Hepatitis B surface antigen positive 24.62 23.62 5 5977 174 79738232
Peripheral T-cell lymphoma unspecified stage IV 24.40 23.62 4 5978 40 79738366
Cytomegalovirus infection 23.65 23.62 22 5960 42622 79695784

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
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
4018769 VANDF

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 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
LEUKERAN HUMAN PRESCRIPTION DRUG LABEL 1 80725-610 TABLET, FILM COATED 2 mg ORAL NDA 25 sections