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Details

Stereochemistry ACHIRAL
Molecular Formula C9H16ClN3O2
Molecular Weight 233.6955
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOMUSTINE

SMILES

C1CCC(CC1)N=C(N(CCCl)N=O)O

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
APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis.
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
Chemotherapy for the treatment of oligodendroglial tumors.
2001 Aug
Melanoma-associated retinopathy: does autoimmunity prolong survival?
2001 Aug
PCV for oligodendroglial tumors: in search of prognostic factors for response and survival.
2001 Aug
Thyroid dysfunction as a late effect in childhood medulloblastoma: a comparison of hyperfractionated versus conventionally fractionated craniospinal radiotherapy.
2001 Aug 1
Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.
2001 Aug-Oct
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
Multiple myeloma in elderly patients: presenting features and outcome.
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
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
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
Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy.
2001 May 1
Lipid association improves the therapeutic index of lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea] to suppress 36B-10 tumor growth in rats.
2001 May 1
Pilot evaluation of 1p and 19q deletions in anaplastic oligodendrogliomas collected by a national cooperative cancer treatment group.
2001 Oct
Medical Research Council adjuvant trial in high-grade gliomas.
2001 Oct 1
Nitric oxide and free stable nitroxyl radicals in the mechanism of biological action of the spin-labeled compounds.
2001 Sep
[Role of adjuvant chemotherapy in the treatment of medulloblastoma in children].
2002
11q23 balanced chromosome aberrations in treatment-related myelodysplastic syndromes and acute leukemia: report from an international workshop.
2002 Apr
Treatment of advanced neuroendocrine tumours using combination chemotherapy with lomustine and 5-fluorouracil.
2002 Aug
Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt.
2002 Aug 1
Pulmonary complications in survivors of childhood and adolescent cancer. A report from the Childhood Cancer Survivor Study.
2002 Dec 1
Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma.
2002 Dec 1
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
Prevention of irradiation-induced glioma cell invasion by temozolomide involves caspase 3 activity and cleavage of focal adhesion kinase.
2002 Mar 15
[Chemo-radiotherapy for malignant brain tumors].
2002 May
Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas.
2002 May 1
Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma.
2002 May 1
Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial.
2002 Oct 1
Complete response of a recurrent, multicentric malignant glioma in a patient treated with phenylbutyrate.
2002 Sep
Radiotherapy alone for lymphocyte-predominant Hodgkin's disease.
2002 Sep-Oct
Low-dose continuous chemotherapy for metastatic melanoma: a phase II trial.
2003 Apr
Feasibility and toxicity of CCNU therapy in elderly patients with glioblastoma multiforme.
2003 Feb
Survival with dacarbazine and fotemustine in newly diagnosed glioblastoma multiforme.
2003 Feb 24
Phase I study of temozolamide (TMZ) combined with procarbazine (PCB) in patients with gliomas.
2003 Jul 21
Myeloid clonogenic assays for comparison of the in vitro toxicity of alkylating agents.
2003 Jun
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
Glioma treatment, radionecrosis, and growth factors. In regard to Levin et al., IJROBP 2002;53:58-66.
2003 Mar 1
Interobserver variability in the radiological assessment of response to chemotherapy in glioma.
2003 Mar 11
Combined modality therapy for poorly differentiated gliomas of the posterior fossa in children: a Children's Cancer Group report.
2003 May
Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma.
2003 May
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 [WHO-DD]
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
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 566
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
NCI_THESAURUS C699
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
NDF-RT N0000000236
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
WHO-VATC QL01AD02
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
WHO-ATC L01AD02
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
NDF-RT N0000175558
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
Code System Code Type Description
EVMPD
SUB08567MIG
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
CAS
13010-47-4
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
MERCK INDEX
M6891
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY Merck Index
PUBCHEM
3950
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
EPA CompTox
13010-47-4
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
DRUG CENTRAL
1596
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
RXCUI
6466
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY RxNorm
HSDB
6519
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
WIKIPEDIA
LOMUSTINE
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
MESH
D008130
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
IUPHAR
7214
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
NCI_THESAURUS
C617
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
DRUG BANK
DB01206
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
USP_CATALOG
1369419
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY USP-RS
ECHA (EC/EINECS)
235-859-2
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
INN
3184
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
FDA UNII
7BRF0Z81KG
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY
ChEMBL
CHEMBL514
Created by admin on Fri Jun 25 21:13:04 UTC 2021 , Edited by admin on Fri Jun 25 21:13:04 UTC 2021
PRIMARY