U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C9H16ClN3O2
Molecular Weight 233.695
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOMUSTINE

SMILES

ClCCN(N=O)C(=O)NC1CCCCC1

InChI

InChIKey=GQYIWUVLTXOXAJ-UHFFFAOYSA-N
InChI=1S/C9H16ClN3O2/c10-6-7-13(12-15)9(14)11-8-4-2-1-3-5-8/h8H,1-7H2,(H,11,14)

HIDE SMILES / InChI

Molecular Formula C9H16ClN3O2
Molecular Weight 233.695
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7f77526b-4c40-409c-82ea-d0f934d89cc2

Lomustine is used in the treatment of certain neoplastic diseases. Although it is generally agreed that lomustine 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. Common adverse reactions include delayed myelosupression, nausea, vomiting, stomatitis, and alopecia.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GLEOSTINE

Approved Use

CeeNU has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following: Brain tumors—both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures. Hodgkin’s disease—secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.

Launch Date

1976
Primary
GLEOSTINE

Approved Use

CeeNU has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following: Brain tumors—both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures. Hodgkin’s disease—secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.

Launch Date

1976
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
8.6 μg/mL
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOMUSTINE plasma
Mus musculus
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2 ng/mL
100 mg/m² single, oral
dose: 100 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
LOMUSTINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
705 μg × min/mL
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOMUSTINE plasma
Mus musculus
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
50%
LOMUSTINE plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
400 mg/m2 single, oral
Highest studied dose
Dose: 400 mg/m2
Route: oral
Route: single
Dose: 400 mg/m2
Co-administed with::
etoposide, i.v(1 g/m2)
ara-C, i.v(4g/m2)
melphalan(140 mg/m2)
Sources:
unhealthy, 36
n = 2
Health Status: unhealthy
Condition: Lymphoma
Age Group: 36
Population Size: 2
Sources:
DLT: Gastrointestinal toxicity, Sinusoidal obstruction syndrome...
Dose limiting toxicities:
Gastrointestinal toxicity (grade 4, 50%)
Sinusoidal obstruction syndrome (grade 4, 50%)
Sources:
300 mg/m2 single, oral
MTD
Dose: 300 mg/m2
Route: oral
Route: single
Dose: 300 mg/m2
Co-administed with::
etoposide, i.v(1 g/m2)
ara-C, i.v(4g/m2)
melphalan(140 mg/m2)
Sources:
unhealthy, 36
n = 6
Health Status: unhealthy
Condition: Lymphoma
Age Group: 36
Population Size: 6
Sources:
DLT: Neurotoxicity...
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Disc. AE: Myelosuppression, Pulmonary toxicity...
AEs leading to
discontinuation/dose reduction:
Myelosuppression (grade 5)
Pulmonary toxicity
Pulmonary fibrosis
Acute leukemia
Myelodysplasia
Hepatotoxicity
Nephrotoxicity
Fetal damage
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal toxicity grade 4, 50%
DLT
400 mg/m2 single, oral
Highest studied dose
Dose: 400 mg/m2
Route: oral
Route: single
Dose: 400 mg/m2
Co-administed with::
etoposide, i.v(1 g/m2)
ara-C, i.v(4g/m2)
melphalan(140 mg/m2)
Sources:
unhealthy, 36
n = 2
Health Status: unhealthy
Condition: Lymphoma
Age Group: 36
Population Size: 2
Sources:
Sinusoidal obstruction syndrome grade 4, 50%
DLT
400 mg/m2 single, oral
Highest studied dose
Dose: 400 mg/m2
Route: oral
Route: single
Dose: 400 mg/m2
Co-administed with::
etoposide, i.v(1 g/m2)
ara-C, i.v(4g/m2)
melphalan(140 mg/m2)
Sources:
unhealthy, 36
n = 2
Health Status: unhealthy
Condition: Lymphoma
Age Group: 36
Population Size: 2
Sources:
Neurotoxicity grade 4, 33.3%
DLT
300 mg/m2 single, oral
MTD
Dose: 300 mg/m2
Route: oral
Route: single
Dose: 300 mg/m2
Co-administed with::
etoposide, i.v(1 g/m2)
ara-C, i.v(4g/m2)
melphalan(140 mg/m2)
Sources:
unhealthy, 36
n = 6
Health Status: unhealthy
Condition: Lymphoma
Age Group: 36
Population Size: 6
Sources:
Acute leukemia Disc. AE
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Fetal damage Disc. AE
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Hepatotoxicity Disc. AE
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Myelodysplasia Disc. AE
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Nephrotoxicity Disc. AE
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Pulmonary fibrosis Disc. AE
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Pulmonary toxicity Disc. AE
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Myelosuppression grade 5
Disc. AE
130 mg/m2 1 times / 6 weeks multiple, oral
Recommended
Dose: 130 mg/m2, 1 times / 6 weeks
Route: oral
Route: multiple
Dose: 130 mg/m2, 1 times / 6 weeks
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Brain tumors|Hodgkin’s lymphoma
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as perpetrator​

Drug as perpetrator​

PubMed

PubMed

TitleDatePubMed
Multidisciplinary management of adult anaplastic oligodendrogliomas and anaplastic mixed oligo-astrocytomas.
2001 Apr
Chemotherapy of low-grade gliomas.
2001 Apr
Adenovirus-mediated expression of HSV1-TK or Fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent CCNU.
2001 Aug
Melanoma-associated retinopathy: does autoimmunity prolong survival?
2001 Aug
Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.
2001 Aug-Oct
Adult medulloblastoma: multiagent chemotherapy.
2001 Jan
Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma.
2001 Jul
Protection of hematopoietic cells from O(6)-alkylation damage by O(6)-methylguanine DNA methyltransferase gene transfer: studies with different O(6)-alkylating agents and retroviral backbones.
2001 Jul
CCNU-dependent potentiation of TRAIL/Apo2L-induced apoptosis in human glioma cells is p53-independent but may involve enhanced cytochrome c release.
2001 Jul 12
[Therapeutic effect on glioblastoma of chemotherapy on the basis of brain irradiation].
2001 Mar
Death receptor-independent cytochrome c release and caspase activation mediate thymidine kinase plus ganciclovir-mediated cytotoxicity in LN-18 and LN-229 human malignant glioma cells.
2001 Mar
Pilot evaluation of 1p and 19q deletions in anaplastic oligodendrogliomas collected by a national cooperative cancer treatment group.
2001 Oct
Intensified PCV-chemotherapy with optional stem cell support in recurrent malignant oligodendroglioma.
2002 Aug
Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt.
2002 Aug 1
Recurrent malignant glioma in adults.
2002 Dec
Long-term follow-up in managing anaplastic astrocytoma by multimodality approach with surgery followed by postoperative radiotherapy and PCV-chemotherapy: phase II trial.
2002 Jun
Evaluation of naphthal-NU, a 2-chloroethylnitrosourea derivative of naphthalimide, as a mixed-function anticancer agent.
2002 Mar
Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial.
2002 Oct 1
Phase I study of fotemustine in pediatric patients with refractory brain tumors.
2002 Sep 15
Survival and prognostic factors of patients with unresectable glioblastoma multiforme.
2003 Apr
Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972.
2003 Apr
Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971.
2003 Jul 1
Myeloid clonogenic assays for comparison of the in vitro toxicity of alkylating agents.
2003 Jun
Glioma treatment, radionecrosis, and growth factors. In regard to Levin et al., IJROBP 2002;53:58-66.
2003 Mar 1
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Lomustine is available in 5 mg, 10 mg, 40 mg, and 100 mg capsules. In individuals with compromised bone marrow function, the dose should be reduced to 100 mg/m2 every 6 weeks.
Recommended dose in adult and pediatric patients is 130 mg/m2 orally every 6 weeks.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: A single dose of Lomustine (40 mg/kg) caused a significant reduction in hepatic mixed-function oxidase activities within 3 days after administration http://www.ncbi.nlm.nih.gov/pubmed/6722931
Alkylation of the nuclear matrix by Lomustine was 1.27 pmoles drug/micrograms protein, whereas carbamoylation by Lomustine was 32.5 pmoles/micrograms.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:15:59 GMT 2023
Edited
by admin
on Fri Dec 15 16:15:59 GMT 2023
Record UNII
7BRF0Z81KG
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOMUSTINE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
LOMUSTINE [USP MONOGRAPH]
Common Name English
1-(2-CHLOROETHYL)-3-CYCLOHEXYL-1-NITROSOUREA [IARC]
Common Name English
1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea
Systematic Name English
LOMUSTINE [HSDB]
Common Name English
LOMUSTINE [EP MONOGRAPH]
Common Name English
CEENU
Brand Name English
CCN-U
Code English
LOMUSTINE [MART.]
Common Name English
CCNU
Code English
LOMUSTINE [VANDF]
Common Name English
UREA, N-(2-CHLOROETHYL)-N'-CYCLOHEXYL-N-NITROSO-
Systematic Name English
LOMUSTINE [USP-RS]
Common Name English
LOMUSTINE [ORANGE BOOK]
Common Name English
Lomustine [WHO-DD]
Common Name English
NSC-79037
Code English
LOMUSTINE [USAN]
Common Name English
LOMUSTINE [MI]
Common Name English
lomustine [INN]
Common Name English
Classification Tree Code System Code
LIVERTOX NBK548631
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
NCI_THESAURUS C699
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
NDF-RT N0000000236
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
WHO-VATC QL01AD02
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
WHO-ATC L01AD02
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
NDF-RT N0000175558
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
Code System Code Type Description
SMS_ID
100000082024
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
EVMPD
SUB08567MIG
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
CAS
13010-47-4
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
MERCK INDEX
m6891
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY Merck Index
PUBCHEM
3950
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
EPA CompTox
DTXSID2023222
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
DRUG CENTRAL
1596
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
DAILYMED
7BRF0Z81KG
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
RXCUI
6466
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY RxNorm
HSDB
6519
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
WIKIPEDIA
LOMUSTINE
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
MESH
D008130
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
IUPHAR
7214
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
NCI_THESAURUS
C617
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
DRUG BANK
DB01206
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
NSC
79037
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
RS_ITEM_NUM
1369419
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
ECHA (EC/EINECS)
235-859-2
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
CHEBI
6520
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
INN
3184
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
FDA UNII
7BRF0Z81KG
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
ChEMBL
CHEMBL514
Created by admin on Fri Dec 15 16:15:59 GMT 2023 , Edited by admin on Fri Dec 15 16:15:59 GMT 2023
PRIMARY
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
Related Record Type Details
IMPURITY -> PARENT
No more than one such impurity (carmustine related compound A, lomustine related compound B, or lomustine related compound C) is greater than 0.2%.
CHROMATOGRAPHIC PURITY (TLC)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
No more than one such impurity (carmustine related compound A, lomustine related compound B, or lomustine related compound C) is greater than 0.2%.
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
No more than one such impurity (carmustine related compound A, lomustine related compound B, or lomustine related compound C) is greater than 0.2%.
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY