Identification

Name
Carmustine
Accession Number
DB00262  (APRD00006)
Type
Small Molecule
Groups
Approved, Investigational
Description

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)

Structure
Thumb
Synonyms
  • BCNU
  • Bicnu (tn)
  • bis-chloroethylnitrosourea
  • Bischloroethyl nitrosourea
  • Carmustina
  • Carmustine
  • Carmustinum
  • N,N'-Bis(2-chloroethyl)-N-nitrosourea
External IDs
NSC-409962
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BiCNUKit100 mg/30mLHeritage Pharmaceuticals Inc.2013-04-04Not applicableUs
BiCNUPowder, for solution100 mgIntravenousMarcan Pharmaceuticals Inc1975-12-31Not applicableCanada
BicnuKit100 mg/30mLE.R. Squibb & Sons, L.L.C.2009-06-012015-09-30Us
GliadelWafer7.7 mg/1IntracavitaryEisai Limited1996-09-242010-05-14Us
GliadelWafer7.7 mg/1IntracavitaryArbor Pharmaceuticals2012-12-13Not applicableUs
Gliadel WaferWafer7.7 mgIntralesionalEisai Limited2002-07-022015-03-02Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarmustineKit100 mg/30mLZydus Pharmaceuticals USA Inc.2018-09-12Not applicableUs
CarmustineKit100 mg/30mLNavinta Llc2018-09-12Not applicableUs
CarmustineKit100 mg/30mLAmneal Biosciences Llc2018-10-22Not applicableUs
International/Other Brands
Becenun / Carmubris / Carustine (Curacell Biotech) / Gliadel / Nitrumon
Categories
UNII
U68WG3173Y
CAS number
154-93-8
Weight
Average: 214.05
Monoisotopic: 213.007181961
Chemical Formula
C5H9Cl2N3O2
InChI Key
DLGOEMSEDOSKAD-UHFFFAOYSA-N
InChI
InChI=1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11)
IUPAC Name
1,3-bis(2-chloroethyl)-3-nitrosourea
SMILES
ClCCNC(=O)N(CCCl)N=O

Pharmacology

Indication

For the treatment of brain tumors, multiple myeloma, Hodgkin's disease and Non-Hodgkin's lymphomas.

Associated Conditions
Pharmacodynamics

Carmustine is one of the nitrosoureas indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in treatment of brain tumors, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphomas. Although it is generally agreed that carmustine alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.

Mechanism of action

Carmustine causes cross-links in DNA and RNA, leading to the inhibition of DNA synthesis, RNA production and RNA translation (protein synthesis). Carmustine also binds to and modifies (carbamoylates) glutathione reductase. This leads to cell death.

TargetActionsOrganism
ADNA
other/unknown
Human
AGlutathione reductase, mitochondrial
inhibitor
Human
ARNA
other/unknown
Human
Absorption

5 to 28% bioavailability

Volume of distribution
Not Available
Protein binding

80%

Metabolism

Hepatic and rapid with active metabolites. Metabolites may persist in the plasma for several days.

Route of elimination

Approximately 60% to 70% of a total dose is excreted in the urine in 96 hours and about 10% as respiratory CO2.

Half life

15-30 minutes

Clearance
Not Available
Toxicity

The oral LD50s in rat and mouse are 20 mg/kg and 45 mg/kg, respectively. Side effects include leukopenia, thrombocytopenia, nausea. Toxic effects include pulmonary fibrosis (20-0%) and bone marrow toxicity.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Carmustine.
(S)-WarfarinThe risk or severity of bleeding can be increased when (S)-Warfarin is combined with Carmustine.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Carmustine is combined with 2-Methoxyethanol.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Carmustine.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Carmustine.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be increased when it is combined with Carmustine.
7-DeazaguanineThe serum concentration of 7-Deazaguanine can be increased when it is combined with Carmustine.
7,9-DimethylguanineThe serum concentration of 7,9-Dimethylguanine can be increased when it is combined with Carmustine.
8-azaguanineThe serum concentration of 8-azaguanine can be increased when it is combined with Carmustine.
8-chlorotheophyllineThe serum concentration of 8-chlorotheophylline can be increased when it is combined with Carmustine.
Food Interactions
  • Echinacea

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014407
KEGG Drug
D00254
KEGG Compound
C06873
PubChem Compound
2578
PubChem Substance
46506980
ChemSpider
2480
BindingDB
50015950
ChEBI
3423
ChEMBL
CHEMBL513
Therapeutic Targets Database
DAP000041
PharmGKB
PA448810
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carmustine
ATC Codes
L01AD01 — Carmustine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (4.55 MB)
MSDS
Download (195 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentLymphoma, B-Cell / Malignant Lymphomas1
1Active Not RecruitingTreatmentMalignant Lymphomas2
1Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1CompletedPreventionLeukemias / Multiple Myeloma (MM)1
1CompletedTreatmentBrain and Central Nervous System Tumors7
1CompletedTreatmentBrain and Central Nervous System Tumors / Neuroblastomas1
1CompletedTreatmentColorectal Cancers1
1CompletedTreatmentMalignant Lymphomas2
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1Not Yet RecruitingTreatmentPediatric Brain Tumor1
1RecruitingTreatmentAdult Burkitt Lymphoma / Adult Diffuse Large B-Cell Lymphoma / Burkitt's Lymphoma / CD20-Positive Neoplastic Cells Present / Indolent Adult Non-Hodgkin Lymphoma / Indolent Non-Hodgkin's Lymphomas / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL) / Recurrent B-Cell Non-Hodgkin Lymphoma / Refractory Mature B-Cell Non-Hodgkin Lymphoma1
1RecruitingTreatmentCastration-Resistant Prostate Carcinoma / Leukemia, Plasma Cell / Prostate Carcinoma Metastatic in the Bone / Recurrent Plasma Cell Myeloma / Stage IV Prostate Cancer1
1RecruitingTreatmentDisseminated Sclerosis1
1RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
1RecruitingTreatmentMature T-Cell and NK-Cell Non-Hodgkin Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma / Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma / Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma1
1RecruitingTreatmentRecurrent Adult Hodgkin's Lymphoma1
1TerminatedTreatmentBrain and Central Nervous System Tumors / Malignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific1
1TerminatedTreatmentRecurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage I Cutaneous T-cell Non-Hodgkin Lymphoma / Stage II Cutaneous T-cell Non-Hodgkin Lymphoma1
1WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus 1 Positive / Stage I Adult Hodgkin Lymphoma / Stage I Adult Non-Hodgkin Lymphoma / Stage II Adult Hodgkin Lymphoma / Stage II Adult Non-Hodgkin Lymphoma / Stage III Adult Hodgkin Lymphoma / Stage III Adult Non-Hodgkin Lymphoma / Stage IV Adult Hodgkin Lymphoma / Stage IV Adult Non-Hodgkin Lymphoma1
1, 2Active Not RecruitingTreatmentAdult Glioblastoma / Adult Gliosarcoma / Glioblastomas / Gliosarcoma1
1, 2Active Not RecruitingTreatmentAdult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / B-cell Adult Acute Lymphoblastic Leukemia / B-Cell Chronic Lymphocytic Leukemia / Chronic Lymphocytic Leukemia (CLL) - Refractory / Cutaneous B-Cell Non-Hodgkin Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Noncutaneous Extranodal Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent B-Cell Non-Hodgkin Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Hodgkin Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Recurrent T-Cell Non-Hodgkin Lymphoma / Refractory B-Cell Non-Hodgkin Lymphoma / Refractory Hairy Cell Leukemia / Refractory Hodgkin Lymphoma / Refractory Mantle Cell Lymphoma / Refractory T-Cell Non-Hodgkin Lymphoma / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / T-cell Adult Acute Lymphoblastic Leukemia / T-Cell Large Granular Lymphocyte Leukemia / Testicular Lymphoma / Waldenström's Macroglobulinemia (WM)1
1, 2Active Not RecruitingTreatmentAdult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Splenic Marginal Zone Lymphoma / Stage III Adult Burkitt Lymphoma / Stage III Adult Diffuse Large Cell Lymphoma / Stage III Adult Diffuse Mixed Cell Lymphoma / Stage III Adult Diffuse Small Cleaved Cell Lymphoma / Stage III Adult Immunoblastic Large Cell Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage III Grade 1 Follicular Lymphoma / Stage III Grade 2 Follicular Lymphoma / Stage III Grade 3 Follicular Lymphoma / Stage III Mantle Cell Lymphoma / Stage III Marginal Zone Lymphoma / Stage III Mycosis Fungoides/Sezary Syndrome / Stage III Small Lymphocytic Lymphoma / Stage IV Adult Burkitt Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma / Stage IV Adult Diffuse Mixed Cell Lymphoma / Stage IV Adult Diffuse Small Cleaved Cell Lymphoma / Stage IV Adult Immunoblastic Large Cell Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma / Stage IV Mantle Cell Lymphoma / Stage IV Marginal Zone Lymphoma / Stage IV Mycosis Fungoides/Sezary Syndrome / Stage IV Small Lymphocytic Lymphoma / Waldenström's Macroglobulinemia (WM)1
1, 2Active Not RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Leukemia, Prolymphocytic / Recurrent Adult Hodgkin's Lymphoma / Recurrent Childhood Hodgkin Lymphoma / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory Childhood Hodgkin Lymphoma / Refractory Hodgkin Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory Small Lymphocytic Lymphoma / T-cell chronic lymphocytic leukaemia / T-Cell Prolymphocytic Leukemia1
1, 2CompletedTreatmentBrain and Central Nervous System Tumors3
1, 2CompletedTreatmentInfection NOS / Multiple Myeloma and Plasma Cell Neoplasm1
1, 2CompletedTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentRecurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage I Cutaneous T-cell Non-Hodgkin Lymphoma / Stage I Mycosis Fungoides and Sezary Syndrome AJCC v7 / Stage II Cutaneous T-cell Non-Hodgkin Lymphoma / Stage II Mycosis Fungoides and Sezary Syndrome AJCC v71
1, 2Not Yet RecruitingTreatmentCD19 Positive / Mantle Cell Lymphoma (MCL) / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Follicular Lymphoma / Refractory B-Cell Non-Hodgkin Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma1
1, 2RecruitingTreatmentHematopoietic Cell Transplantation Recipient / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Non-Hodgkin Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Marginal Zone Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory Transformed Indolent Non-Hodgkin Lymphoma1
1, 2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma / Plasmablastic Lymphoma / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Non-Hodgkin Lymphoma / Recurrent Burkitt Lymphoma / Recurrent Follicular Lymphoma / Stage III Follicular Lymphoma / Stage III Mantle Cell Lymphoma / Stage IV Follicular Lymphoma / Stage IV Mantle Cell Lymphoma1
1, 2WithdrawnTreatmentCancer, Breast1
1, 2WithdrawnTreatmentGlioblastoma Multiforme (GBM)1
2Active Not RecruitingTreatmentAdult Diffuse Large B-Cell Lymphoma / B-cell Non-Hodgkin's Lymphomas / Follicular Lymphoma (FL) / Mantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL) / T-Cell Non-Hodgkin Lymphoma1
2Active Not RecruitingTreatmentDiffuse Large Cell Lymphoma / Malignant Lymphomas1
2Active Not RecruitingTreatmentGlioblastoma Multiforme (GBM) / Gliosarcoma1
2Active Not RecruitingTreatmentMalignant Lymphomas2
2CompletedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Oligodendroglioma (AO) / Glioblastoma Multiforme (GBM) / Mixed Gliomas / Recurrent Brain Tumors1
2CompletedTreatmentBrain and Central Nervous System Tumors8
2CompletedTreatmentBrain and Central Nervous System Tumors / Head and Neck Carcinoma / Malignant Lymphomas1
2CompletedTreatmentCD20 Positive / Hematopoietic and Lymphoid Cell Neoplasm / Lymphocytic Neoplasm / Malignant Lymphomas1
2CompletedTreatmentCancer of the Ovary1
2CompletedTreatmentCancer, Breast / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Testicular germ cell tumour / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific1
2CompletedTreatmentCentral Nervous System Lymphoma1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias2
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentDisseminated Sclerosis / Relapsing Remitting Multiple Sclerosis (RRMS)1
2CompletedTreatmentGliomas1
2CompletedTreatmentGraft Versus Host Disease (GVHD) / Malignant Lymphomas1
2CompletedTreatmentHodgkins Disease (HD) / Lymphoma, Hodgkin Disease / Lymphoma, Hodgkins / Malignant Lymphomas1
2CompletedTreatmentHodgkins Disease (HD) / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Malignant Lymphomas1
2CompletedTreatmentLeukemias2
2CompletedTreatmentLeukemias / Malignant Lymphomas2
2CompletedTreatmentLymphoma, Large Cell, Diffuse1
2CompletedTreatmentMalignant Lymphomas20
2CompletedTreatmentMalignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm1
2CompletedTreatmentMelanoma (Skin)2
2CompletedTreatmentMetastatic Brain Tumors1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm3
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)2
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRecurrent Adult Brain Tumor1
2CompletedTreatmentSarcomas1
2Not Yet RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentAutoimmune Diseases / Autoimmune Disorders1
2RecruitingTreatmentB-Cell Prolymphocytic Leukemia / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Hypodiploidy / Leukemia, Plasma Cell / Loss of Chromosome 17p / Progression of Multiple Myeloma or Plasma Cell Leukemia / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Non-Hodgkin Lymphoma / Recurrent Childhood Hodgkin Lymphoma / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Plasma Cell Myeloma / Recurrent Small Lymphocytic Lymphoma / Refractory Childhood Hodgkin Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory Plasma Cell Myeloma / Refractory Small Lymphocytic Lymphoma / T(14;16) / T(4;14) / T-Cell Prolymphocytic Leukemia / Waldenström's Macroglobulinemia (WM)1
2RecruitingTreatmentB-cell Non-Hodgkin's Lymphomas / Mantle Cell Lymphoma (MCL) / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Follicular Lymphoma / Recurrent Indolent Adult Non-Hodgkin Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Indolent Adult Non-Hodgkin Lymphoma1
2RecruitingTreatmentDouble-hit Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL) / Peripheral T Cell Lymphoma (PTCL)1
2RecruitingTreatmentLymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL) / Refractory Diffuse Large B-cell Lymphoma (DLBCL) / Relapsed Diffuse Large B-cell Lymphoma (DLBCL)1
2RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2RecruitingTreatmentMultiple Myeloma (MM)1
2RecruitingTreatmentResidual Tumor / Triple-Negative Invasive Breast Carcinoma1
2TerminatedDiagnosticMalignant Lymphomas1
2TerminatedTreatmentAcute Lymphocytic Leukemia (ALL) / Acute Myelogenous Leukaemia (AML) / Aplastic Anaemia (AA) / Chronic Chronic myelogenous leukemia / Chronic Lymphocytic Leukaemia (CLL) / Hodgkins Disease (HD) / Multiple Myeloma (MM) / Myelodysplastic Syndrome / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentBlood and Marrow Transplant (BMT) / Diffuse Large B-Cell / Lymphoma, B-Cell / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Lymphomas: Non-Hodgkin / Malignant Lymphoma, Non-Hodgkin / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Unusual Cancers of Childhood1
2TerminatedTreatmentGlioblastoma Multiforme (GBM) / Gliosarcoma / Malignant Gliomas1
2TerminatedTreatmentGlioblastoma Multiforme (GBM) / High-Grade Gliomas1
2TerminatedTreatmentHematologic Diseases1
2TerminatedTreatmentMelanoma Metastatic1
2TerminatedTreatmentMultiple Myeloma (MM)1
2TerminatedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
2TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Unknown StatusSupportive CareChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
2Unknown StatusTreatmentMalignant Lymphomas2
2Unknown StatusTreatmentMalignant Lymphomas / Small Intestine Cancer1
2Unknown StatusTreatmentMantle Cell Lymphoma (MCL)1
2Unknown StatusTreatmentNewly Diagnosed Supratentorial Malignant Glioma1
2Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Unknown StatusTreatmentPrimary Non Hodgkin Lymphoma of the Central Nervous System1
2WithdrawnTreatmentAdult Brain Glioblastoma / Recurrent Adult Brain Neoplasm1
2WithdrawnTreatmentBrain and Central Nervous System Tumors1
2WithdrawnTreatmentMalignant Lymphomas2
2, 3CompletedTreatmentMalignant Lymphomas1
3CompletedTreatmentAstrocytomas / Glioblastoma Multiforme (GBM) / Gliomas1
3CompletedTreatmentBrain and Central Nervous System Tumors2
3CompletedTreatmentCancer, Breast1
3CompletedTreatmentGlioblastoma Multiforme (GBM)1
3CompletedTreatmentGlioblastomas1
3CompletedTreatmentLeukemias / Malignant Lymphomas1
3CompletedTreatmentLeukemias / Neutropenias1
3CompletedTreatmentLymphoma, Large-Cell, Diffuse1
3CompletedTreatmentMalignant Lymphomas5
3CompletedTreatmentMalignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System1
3CompletedTreatmentMultiple Myeloma (MM)2
3CompletedTreatmentStage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
3RecruitingTreatmentActivated B-Cell-Like Diffuse Large B-Cell Lymphoma / B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma / Diffuse Large B-Cell Lymphoma Activated B-Cell Type / Diffuse Large B-Cell Lymphoma, Not Otherwise Specified / High Grade B-Cell Lymphoma, Not Otherwise Specified / Recurrent Burkitt Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Refractory Burkitt Lymphoma / Refractory Diffuse Large B Cell Lymphoma1
3TerminatedTreatmentAnaplastic Astrocytoma (AA) / Glioblastomas1
3TerminatedTreatmentCancer, Breast1
3TerminatedTreatmentMalignant Lymphomas2
3TerminatedTreatmentRecurrent Diffuse Large B-Cell Lymphoma / Refractory Diffuse Large B Cell Lymphoma1
3Unknown StatusTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Oligoastrocytoma / Anaplastic Oligodendroglioma (AO) / Glioblastomas1
3Unknown StatusTreatmentBrain and Central Nervous System Tumors1
3Unknown StatusTreatmentIPI≥2 / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
3Unknown StatusTreatmentMalignant Lymphomas4
3Unknown StatusTreatmentMantle Cell Lymphoma (MCL)1
3Unknown StatusTreatmentMultiple Myeloma and Plasma Cell Neoplasm2
Not AvailableActive Not RecruitingTreatmentHodgkins Disease (HD) / Malignant Lymphomas1
Not AvailableActive Not RecruitingTreatmentMalignant Lymphomas1
Not AvailableCompletedTreatmentAdult Acute Lymphoblastic Leukemia in Remission / Adult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Nasal Type Extranodal NK/T-Cell Lymphoma / Childhood Acute Lymphoblastic Leukemia in Remission / Childhood Acute Myeloid Leukemia in Remission / Childhood Burkitt Lymphoma / Childhood Diffuse Large Cell Lymphoma / Childhood Immunoblastic Large Cell Lymphoma / Childhood Nasal Type Extranodal NK/T-cell Lymphoma / Chronic Lymphocytic Leukemia (CLL) - Refractory / Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET) / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Peripheral T-Cell Lymphoma (PTCL) / Plasma Cell Neoplasms / Primary Systemic Amyloidosis / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Childhood Anaplastic Large Cell Lymphoma / Recurrent Childhood Grade III Lymphomatoid Granulomatosis / Recurrent Childhood Large Cell Lymphoma / Recurrent Childhood Lymphoblastic Lymphoma / Recurrent Childhood Small Noncleaved Cell Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Malignant Testicular Germ Cell Tumor / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Neuroblastoma / Recurrent Small Lymphocytic Lymphoma / Recurrent/Refractory Childhood Hodgkin Lymphoma / Refractory Multiple Myeloma / Regional Neuroblastoma / Splenic Marginal Zone Lymphoma / Testicular Lymphoma / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific / Waldenström's Macroglobulinemia (WM)1
Not AvailableCompletedTreatmentMalignant Lymphomas1
Not AvailableRecruitingTreatmentLymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
Not AvailableUnknown StatusTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Oligoastrocytoma / Anaplastic Oligodendroglioma (AO) / Glioblastomas1
Not AvailableWithdrawnTreatmentAdult Nasal Type Extranodal NK/T-Cell Lymphoma / AIDS-Related Diffuse Large Cell Lymphoma / AIDS-Related Diffuse Mixed Cell Lymphoma / AIDS-Related Diffuse Small Cleaved Cell Lymphoma / AIDS-related Immunoblastic Large Cell Lymphoma / AIDS-Related Lymphoblastic Lymphoma / AIDS-related Peripheral/Systemic Lymphoma / AIDS-related Small Noncleaved Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Cutaneous B-Cell Non-Hodgkin Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / HIV-associated Hodgkin Lymphoma / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Noncutaneous Extranodal Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Refractory Hairy Cell Leukemia / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / Stage I AIDS-related Lymphoma / Stage II AIDS-related Lymphoma / Stage III AIDS-related Lymphoma / Stage IV AIDS-related Lymphoma / T-Cell Large Granular Lymphocyte Leukemia / Testicular Lymphoma / Waldenström's Macroglobulinemia (WM)1

Pharmacoeconomics

Manufacturers
  • Eisai inc
  • Bristol laboratories inc div bristol myers co
Packagers
  • Bristol-Myers Squibb Co.
  • Eisai Inc.
  • Mead Johnson and Co.
  • MGI Pharma
Dosage forms
FormRouteStrength
Kit100 mg/30mL
Powder, for solutionIntravenous100 mg
WaferIntracavitary7.7 mg/1
WaferIntralesional7.7 mg
Prices
Unit descriptionCostUnit
Gliadel Wafer 8 7.7 mg Wafers Box22611.26USD box
Gliadel wafer3667.95USD each
Bicnu 100 mg vial205.69USD vial
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Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)31 °CPhysProp
water solubility4000 mg/L (at 25 °C)MERCK (1989)
logP1.53HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility1.53 mg/mLALOGPS
logP1.24ALOGPS
logP1.02ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)11.96ChemAxon
pKa (Strongest Basic)-5.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area61.77 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity46.98 m3·mol-1ChemAxon
Polarizability18.8 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9533
Caco-2 permeable-0.5621
P-glycoprotein substrateNon-substrate0.7552
P-glycoprotein inhibitor INon-inhibitor0.797
P-glycoprotein inhibitor IINon-inhibitor0.8778
Renal organic cation transporterNon-inhibitor0.8177
CYP450 2C9 substrateNon-substrate0.7656
CYP450 2D6 substrateNon-substrate0.8491
CYP450 3A4 substrateNon-substrate0.672
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9031
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9131
Ames testAMES toxic0.9577
CarcinogenicityCarcinogens 0.688
BiodegradationNot ready biodegradable0.5596
Rat acute toxicity3.9975 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7278
hERG inhibition (predictor II)Non-inhibitor0.919
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as nitrosoureas. These are compounds containing a nitro group and an urea group N-N linked together, with the general structure R1N(R2)C(=O)N(R3)N=O.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic carbonic acids and derivatives
Sub Class
Ureas
Direct Parent
Nitrosoureas
Alternative Parents
Semicarbazides / Nitrosamides / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Alkyl chlorides
Substituents
Nitrosourea / Semicarbazide / Nitrosamide / Organic n-nitroso compound / Organic nitroso compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Alkyl chloride
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
organochlorine compound, N-nitrosoureas (CHEBI:3423)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Other/unknown
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. 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. [PubMed:17016423]
  2. Johannessen TC, Bjerkvig R, Tysnes BB: DNA repair and cancer stem-like cells--potential partners in glioma drug resistance? Cancer Treat Rev. 2008 Oct;34(6):558-67. doi: 10.1016/j.ctrv.2008.03.125. Epub 2008 May 22. [PubMed:18501520]
  3. Lin SH, Kleinberg LR: Carmustine wafers: localized delivery of chemotherapeutic agents in CNS malignancies. Expert Rev Anticancer Ther. 2008 Mar;8(3):343-59. doi: 10.1586/14737140.8.3.343. [PubMed:18366283]
  4. Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE: Alkylation damage in DNA and RNA--repair mechanisms and medical significance. DNA Repair (Amst). 2004 Nov 2;3(11):1389-407. [PubMed:15380096]
  5. Zhang Q, Ohannesian DW, Kreklau EL, Erickson LC: Modulation of 1,3-bis-(2-chloroethyl)-1-nitrosourea resistance in human tumor cells using hammerhead ribozymes designed to degrade O6-methylguanine DNA methyltransferase mRNA. J Pharmacol Exp Ther. 2001 Jul;298(1):141-7. [PubMed:11408535]
  6. He YH, Xu Y, Kobune M, Wu M, Kelley MR, Martin WJ 2nd: Escherichia coli FPG and human OGG1 reduce DNA damage and cytotoxicity by BCNU in human lung cells. Am J Physiol Lung Cell Mol Physiol. 2002 Jan;282(1):L50-5. [PubMed:11741815]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nadp binding
Specific Function
Maintains high levels of reduced glutathione in the cytosol.
Gene Name
GSR
Uniprot ID
P00390
Uniprot Name
Glutathione reductase, mitochondrial
Molecular Weight
56256.565 Da
References
  1. Akella SS, Harris C: Pyridine nucleotide flux and glutathione oxidation in the cultured rat conceptus. Reprod Toxicol. 1999 May-Jun;13(3):203-13. [PubMed:10378469]
  2. Kirsch JD, Yi AK, Spitz DR, Krieg AM: Accumulation of glutathione disulfide mediates NF-kappaB activation during immune stimulation with CpG DNA. Antisense Nucleic Acid Drug Dev. 2002 Oct;12(5):327-40. [PubMed:12477282]
  3. Vallyathan V, Mega JF, Shi X, Dalal NS: Enhanced generation of free radicals from phagocytes induced by mineral dusts. Am J Respir Cell Mol Biol. 1992 Apr;6(4):404-13. [PubMed:1312851]
  4. Brodie AE, Reed DJ: Glutathione disulfide reduction in tumor mitochondria after t-butyl hydroperoxide treatment. Chem Biol Interact. 1992 Sep 28;84(2):125-32. [PubMed:1394620]
  5. Jopperi-Davis KS, Park MS, Rogers LK, Backes CH Jr, Lim IK, Smith CV: Compartmental inhibition of hepatic glutathione reductase activities by 1,3-bis(2-chloroethyl)-N-nitrosourea (BCNU) in Sprague-Dawley and Fischer-344 rats. Toxicol Lett. 2004 Mar 7;147(3):219-28. [PubMed:15104113]
  6. Doroshenko N, Doroshenko P: The glutathione reductase inhibitor carmustine induces an influx of Ca2+ in PC12 cells. Eur J Pharmacol. 2004 Aug 16;497(1):17-24. [PubMed:15321730]
  7. Powell SR, Puglia CD: Effect of inhibition of glutathione reductase by carmustine on central nervous system oxygen toxicity. J Pharmacol Exp Ther. 1987 Jan;240(1):111-7. [PubMed:3806383]
  8. Puglia CD, Powell SR: Inhibition of cellular antioxidants: a possible mechanism of toxic cell injury. Environ Health Perspect. 1984 Aug;57:307-11. [PubMed:6094175]
3. RNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Other/unknown
References
  1. Lin SH, Kleinberg LR: Carmustine wafers: localized delivery of chemotherapeutic agents in CNS malignancies. Expert Rev Anticancer Ther. 2008 Mar;8(3):343-59. doi: 10.1586/14737140.8.3.343. [PubMed:18366283]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on December 18, 2018 09:05