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

Stem definitionDrug idCAS RN
antineoplastic, alkylating agents, (beta-chloroethyl)amine derivatives 512 154-93-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • carmustine
  • becenun
  • carmubris
  • carmustin
  • nitrumon
A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
  • Molecular weight: 214.05
  • Formula: C5H9Cl2N3O2
  • CLOGP: 1.32
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 61.77
  • ALOGS: -2.15
  • ROTB: 5

  • 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) 3.80 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) 0.55 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 11.50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.20 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 78 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.23 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.37 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 7, 1977 FDA EMCURE PHARMS LTD

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
Myelodysplastic syndrome 217.42 36.65 65 2506 15646 46667845
Malignant transformation 142.49 36.65 23 2548 292 46683199
Brain oedema 127.64 36.65 41 2530 12437 46671054
Febrile neutropenia 104.95 36.65 65 2506 94562 46588929
Mucosal inflammation 100.60 36.65 47 2524 38929 46644562
Acute myeloid leukaemia 99.18 36.65 36 2535 15742 46667749
Stem cell transplant 81.39 36.65 19 2552 1747 46681744
Second primary malignancy 77.09 36.65 24 2547 6560 46676931
Pneumocephalus 60.88 36.65 10 2561 142 46683349
Thrombocytopenia 57.85 36.65 51 2520 126530 46556961
Enterococcal infection 51.66 36.65 18 2553 6969 46676522
Intracranial hypotension 46.91 36.65 9 2562 320 46683171
Progressive multifocal leukoencephalopathy 46.57 36.65 19 2552 11327 46672164
Venoocclusive disease 44.69 36.65 12 2559 1944 46681547
Cardiomyopathy acute 44.04 36.65 8 2563 210 46683281
Pneumocystis jirovecii pneumonia 41.17 36.65 19 2552 15229 46668262
Chronic myelomonocytic leukaemia 40.88 36.65 8 2563 316 46683175
JC virus infection 37.05 36.65 10 2561 1652 46681839

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
Myelodysplastic syndrome 329.19 32.26 120 4582 18658 29929118
Venoocclusive liver disease 243.34 32.26 74 4628 6539 29941237
Malignant transformation 225.17 32.26 45 4657 668 29947108
Acute myeloid leukaemia 167.70 32.26 73 4629 17933 29929843
Febrile neutropenia 146.29 32.26 126 4576 106567 29841209
Brain oedema 127.68 32.26 54 4648 12344 29935432
Off label use 126.72 32.26 174 4528 249116 29698660
Second primary malignancy 123.80 32.26 44 4658 6312 29941464
Pneumocephalus 118.57 32.26 19 4683 68 29947708
Blood stem cell transplant failure 88.49 32.26 19 4683 406 29947370
Basal cell carcinoma 78.81 32.26 42 4660 16026 29931750
Mucosal inflammation 72.31 32.26 50 4652 30444 29917332
Venoocclusive disease 62.29 32.26 21 4681 2569 29945207
Malignant neoplasm progression 61.87 32.26 66 4636 72221 29875555
Aspergillus infection 59.56 32.26 30 4672 10184 29937592
Myositis 59.11 32.26 30 4672 10347 29937429
Hepatic infection fungal 55.60 32.26 11 4691 154 29947622
Transformation to acute myeloid leukaemia 55.11 32.26 14 4688 632 29947144
Bronchopulmonary aspergillosis 54.35 32.26 30 4672 12254 29935522
Product use in unapproved indication 53.93 32.26 62 4640 73631 29874145
Diffuse large B-cell lymphoma 51.57 32.26 25 4677 7816 29939960
Stem cell transplant 50.14 32.26 17 4685 2114 29945662
Metastases to muscle 47.05 32.26 10 4692 203 29947573
Metastases to retroperitoneum 46.82 32.26 10 4692 208 29947568
Febrile bone marrow aplasia 44.92 32.26 23 4679 8074 29939702
Human herpesvirus 8 infection 44.63 32.26 12 4690 677 29947099
Neutropenic sepsis 42.75 32.26 25 4677 11384 29936392
Metastases to spleen 42.31 32.26 10 4692 333 29947443
Expanded disability status scale score increased 41.97 32.26 9 4693 191 29947585
Cytomegalovirus infection 40.70 32.26 32 4670 23642 29924134
Metastases to bone marrow 38.39 32.26 10 4692 499 29947277
Enteritis 37.22 32.26 19 4683 6626 29941150
B-cell lymphoma recurrent 36.07 32.26 10 4692 633 29947143
Intentional product use issue 34.21 32.26 35 4667 36405 29911371
Staphylococcal infection 33.90 32.26 32 4670 30192 29917584
Intracranial hypotension 33.86 32.26 8 4694 266 29947510
Retinal haemorrhage 33.85 32.26 16 4686 4727 29943049
Pneumocystis jirovecii pneumonia 33.50 32.26 25 4677 17095 29930681
Cytopenia 33.35 32.26 19 4683 8237 29939539

Pharmacologic Action:

SourceCodeDescription
ATC L01AD01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ALKYLATING AGENTS
Nitrosoureas
FDA MoA N0000000236 Alkylating Activity
FDA EPC N0000175558 Alkylating Drug
CHEBI has role CHEBI:35610 cytostatic
MeSH PA D000477 Alkylating Agents
MeSH PA D000970 Antineoplastic Agents
MeSH PA D018906 Antineoplastic Agents, Alkylating
MeSH PA D009676 Noxae

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Glioma, malignant indication 74532006
Diffuse non-Hodgkin's lymphoma, large cell indication 109969005
Multiple myeloma indication 109989006 DOID:9538
Hodgkin's disease indication 118599009
Non-Hodgkin's lymphoma indication 118601006
Glioblastoma multiforme of brain indication 276828006 DOID:3073
Malignant neoplasm of brain indication 428061005 DOID:1319
Astrocytoma, anaplastic off-label use 55353007 DOID:3078
Allogeneic bone marrow transplantation off-label use 58390007
Mycosis fungoides off-label use 118618005
Cerebral edema contraindication 2032001
Mycosis contraindication 3218000 DOID:1564
Meningitis contraindication 7180009 DOID:9471
Disorder of lung contraindication 19829001 DOID:850
Retinal hemorrhage contraindication 28998008
Viral disease contraindication 34014006 DOID:934
Infectious disease contraindication 40733004
Fibrosis of lung contraindication 51615001 DOID:3770
Epilepsy contraindication 84757009 DOID:1826
Leukopenia contraindication 84828003 DOID:615
Bacterial infectious disease contraindication 87628006
Kidney disease contraindication 90708001 DOID:557
Acute leukemia, disease contraindication 91855006 DOID:12603
Liver function tests abnormal contraindication 166603001
Obstructive hydrocephalus contraindication 230746009 DOID:14159
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001
Abscess of brain contraindication 441806004
Protozoal Infection contraindication
Significant Bleeding contraindication
Pulmonary Infiltrates contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.09 acidic

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
Glutathione reductase, mitochondrial Enzyme INHIBITOR IC50 5.09 CHEMBL CHEMBL
DNA DNA OTHER DRUG LABEL DRUG LABEL

External reference:

IDSource
4020993 VUID
N0000148463 NUI
D00254 KEGG_DRUG
4018136 VANDF
4020993 VANDF
C1516301 UMLSCUI
CHEBI:3423 CHEBI
CHEMBL513 ChEMBL_ID
DB00262 DRUGBANK_ID
D002330 MESH_DESCRIPTOR_UI
2959 INN_ID
2578 PUBCHEM_CID
6800 IUPHAR_LIGAND_ID
U68WG3173Y UNII
2105 RXNORM
251354 MMSL
4360 MMSL
d01342 MMSL
002640 NDDF
387281007 SNOMEDCT_US
51326002 SNOMEDCT_US
786790001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Gliadel HUMAN PRESCRIPTION DRUG LABEL 1 24338-050 WAFER 7.70 mg INTRACAVITARY NDA 25 sections