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

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

2.07964799E11
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

2.07964799E11
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
[Post-operative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of German prospective randomised trial HIT'91].
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
Adults with newly diagnosed high-grade gliomas.
2001 Dec
Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia.
2001 Feb 15
Bleomycin, lomustine, cyclophosphamide, vincristine, procarbazine and prednisone (BLEO-CCVPP) in patients with Hodgkin's disease who relapsed after radiotherapy alone: a long-term follow-up study of the Eastern Cooperative Oncology Group (E3481).
2001 Jan
Spin labelled nitrosoureas and triazenes and their non-labelled clinically used analogues--a comparative study on their physicochemical properties and antimelanomic effects.
2001 Jan 16
Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma.
2001 Jul
Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer.
2001 Jun
PCV chemotherapy for recurrent glioblastoma multiforme.
2001 Jun 26
[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
Medical Research Council adjuvant trial in high-grade gliomas.
2001 Oct 1
The effectiveness of the O(6)-alkylguanine-DNA alkyltransferase encoded by the ogt(ST) gene from S. typhimurium in protection against alkylating drugs, resistance to O(6)-benzylguanine and sensitisation to dibromoalkane genotoxicity.
2001 Oct 18
Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt.
2002 Aug 1
Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91.
2002 Feb 1
High expression levels of collagenase-1 and stromelysin-1 correlate with shorter disease-free survival in human metastatic melanoma.
2002 Feb 1
Treatment of intracranial metastatic esthesioneuroblastoma.
2002 Jan 1
Treatment of intracranial metastatic esthesioneuroblastoma.
2002 Jul 15
Evaluation of naphthal-NU, a 2-chloroethylnitrosourea derivative of naphthalimide, as a mixed-function anticancer agent.
2002 Mar
Concurrent modified PCV chemotherapy and radiotherapy in newly diagnosed grade IV astrocytoma.
2002 May
NO-mediated chemoresistance in C6 glioma cells.
2002 May
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
Dramatic response to chemotherapy in oligodendroglial gliomatosis cerebri.
2003 Jan 14
High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy.
2003 Jun 15
Irinotecan in the treatment of glioma patients: current and future studies of the North Central Cancer Treatment Group.
2003 May 1
Role of mismatch repair in the induction of chromosomal aberrations and sister chromatid exchanges in cells treated with different chemotherapeutic agents.
2003 Sep
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.
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 Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
NCI_THESAURUS C699
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
NDF-RT N0000000236
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
WHO-VATC QL01AD02
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
WHO-ATC L01AD02
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
NDF-RT N0000175558
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
Code System Code Type Description
SMS_ID
100000082024
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
EVMPD
SUB08567MIG
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
CAS
13010-47-4
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
MERCK INDEX
M6891
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY Merck Index
PUBCHEM
3950
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
EPA CompTox
DTXSID2023222
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
DRUG CENTRAL
1596
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
DAILYMED
7BRF0Z81KG
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
RXCUI
6466
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY RxNorm
HSDB
6519
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
WIKIPEDIA
LOMUSTINE
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
MESH
D008130
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
IUPHAR
7214
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
NCI_THESAURUS
C617
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
DRUG BANK
DB01206
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
NSC
79037
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
RS_ITEM_NUM
1369419
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
ECHA (EC/EINECS)
235-859-2
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
CHEBI
6520
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
INN
3184
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
FDA UNII
7BRF0Z81KG
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY
ChEMBL
CHEMBL514
Created by admin on Wed Jul 05 23:43:07 UTC 2023 , Edited by admin on Wed Jul 05 23:43:07 UTC 2023
PRIMARY