Lomustine

Lomustine
Clinical data


Trade names	Gleostine
AHFS/Drugs.com	Monograph
MedlinePlus	a682207
Pregnancy category	D
Routes of administration	Oral (capsules)
ATC code	L01AD02 (WHO)
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Bioavailability	~100%
Protein binding	50%
Metabolism	Liver
Metabolites	Monoxydroxylated metabolites, trans-4-hydroxy-CCNU, cis-4-hydroxy-CCNU^[1]
Biological half-life	16–48 hours (metabolites)
Identifiers
IUPAC name N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea
Synonyms	1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea
CAS Number	13010-47-4^Y
PubChem (CID)	3950
IUPHAR/BPS	7214
DrugBank	DB01206^Y
ChemSpider	3813^Y
UNII	7BRF0Z81KG^Y
KEGG	D00363^Y
ChEBI	CHEBI:6520^N
ChEMBL	CHEMBL514^Y
ECHA InfoCard	100.032.585
Chemical and physical data
Formula	C₉H₁₆ClN₃O₂
Molar mass	233.695 g/mol
3D model (Jmol)	Interactive image
Melting point	90 °C (194 °F)
SMILES O=C(NC1CCCCC1)N(N=O)CCCl
InChI 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)^Y Key:GQYIWUVLTXOXAJ-UHFFFAOYSA-N^Y
^NY (what is this?) (verify)

Lomustine (INN), abbreviated CCNU (original brand name (formerly available) is CeeNU, now marketed as Gleostine), is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug^[2] and thus crosses the blood-brain barrier. This property makes it ideal for treating brain tumors, which is its primary use. Lomustine has a long time to nadir (the time when white blood cells reach their lowest number).

Unlike carmustine, lomustine is administered orally. It is a monofunctional alkylating agent, alkylates both DNA and RNA, has the ability to cross-link DNA.^[3] As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.^[4] Lomustine is cell-cycle nonspecific.

Rebranding

In 2014, the drug was re-launched and rebranded as Gleostine, manufactured by NextSource Biotechnology.^[5]^[6]

References

↑ Lee, FY; Workman, P; Roberts, JT; Bleehen, NM (1985). "Clinical Pharmacokinetics of Oral CCNU (lomustine)". Cancer Chemotherapy and Pharmacology. 14 (2): 125–31. doi:10.1007/bf00434350. PMID 3971475. |access-date= requires |url= (help)
↑ "BC Cancer Agency Cancer Drug Manual. Lomustine (CCNU; CeeNU)" (PDF). Retrieved 15 July 2016.
↑ Pizzo, PA; Poplack, DG, eds. (2006). Principles and Practice of Pediatric Oncology (5 ed.). Philadelphia: Lippincott Williams & Wilkins. p. 300. ISBN 9780781754927. |access-date= requires |url= (help)
↑ "Gleostine (lomustine) Capsules, for Oral Use. Full Prescribing Information" (PDF). NextSource Biotechnology, LLC. Retrieved 15 July 2016.
↑ "NextSource Biotechnology Gains FDA Approval for Use of Tradename Gleostine (lomustine), an Anti-Cancer Chemotherapy Agent". www.prnewswire.com. NextSource Biotechnology. Retrieved 15 July 2016.
↑ "Gleostine (lomustine) Capsules — Healthcare Providers". NextSource Biotechnology. Retrieved 15 July 2016.

External links

CeeNu (lomustine) Capsules data sheet published by the FDA
Lomustine at the US National Library of Medicine Medical Subject Headings (MeSH)
DDB 29525

Intracellular chemotherapeutic agents / antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine^# Vincristine^# Vinflunine^§ Vindesine Vinorelbine)

Block microtubule disassembly	Taxanes (Cabazitaxel Docetaxel^# Larotaxel Ortataxel^† Paclitaxel^# Tesetaxel) Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	Dihydrofolate reductase inhibitor (Aminopterin Methotrexate^# Pemetrexed Pralatrexate) Thymidylate synthase inhibitor (Raltitrexed Pemetrexed)

Purine	Adenosine deaminase inhibitor (Pentostatin) Halogenated/ribonucleotide reductase inhibitors (Cladribine Clofarabine Fludarabine) Nelarabine Thiopurine (Thioguanine^# Mercaptopurine^#)

Pyrimidine	Thymidylate synthase inhibitor (Fluorouracil^# Capecitabine Tegafur (+gimeracil/oteracil) Carmofur Floxuridine) DNA polymerase inhibitor (Cytarabine^#) Ribonucleotide reductase inhibitor (Gemcitabine) Hypomethylating agent (Azacitidine Decitabine)

Deoxyribonucleotide	Ribonucleotide reductase inhibitor (Hydroxycarbamide)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Camptothecin Cositecan^† Belotecan Gimatecan Exatecan Irinotecan Lurtotecan^‡ Silatecan^§ Topotecan Rubitecan^‡)

II	Podophyllum (Etoposide^# Teniposide)

II+Intercalation	Anthracyclines (Aclarubicin Daunorubicin^# Doxorubicin^# Epirubicin Idarubicin Amrubicin^† Pirarubicin Valrubicin Zorubicin) Anthracenediones (Mitoxantrone Pixantrone)

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Mechlorethamine Cyclophosphamide^# (Ifosfamide Trofosfamide) Chlorambucil^# (Melphalan Prednimustine) Bendamustine Uramustine Estramustine Nitrosoureas: Carmustine Lomustine (Semustine) Fotemustine Nimustine Ranimustine Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan Treosulfan) Aziridines: Carboquone ThioTEPA Triaziquone Triethylenemelamine

Platinum-based	Carboplatin Cisplatin Dicycloplatin Nedaplatin Oxaliplatin Satraplatin

Nonclassical	Hydrazines (Procarbazine^#) Triazenes (Dacarbazine^# Temozolomide) Altretamine Mitobronitol Pipobroman

Intercalation	Streptomyces (Actinomycin^# Bleomycin^# Mitomycin Plicamycin)

Photosensitizers/PDT

Other

Enzyme inhibitors	FI (Tipifarnib^§) CDK inhibitors (Alvocidib^† Seliciclib^† Palbociclib) PrI Bortezomib Carfilzomib Ixazomib PhI (Anagrelide) IMPDI (Tiazofurin^§) LI (Masoprocol) PARP inhibitor (Olaparib) HDAC (Belinostat Panobinostat Romidepsin Vorinostat) PIKI (Idelalisib)

Receptor antagonists	ERA (Atrasentan) Retinoid X receptor (Bexarotene) Sex steroid (Testolactone)

Other/ungrouped	Amsacrine Trabectedin Retinoids (Alitretinoin Tretinoin) Arsenic trioxide Asparagine depleters (Asparaginase^#/Pegaspargase) Celecoxib Demecolcine Elesclomol^§ Elsamitrucin Etoglucid Lonidamine Lucanthone Mitoguazone Mitotane Oblimersen^† Omacetaxine mepesuccinate Eribulin

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

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