eflornithine   Click here for help

GtoPdb Ligand ID: 5176

Synonyms: 2-(difluoromethyl)ornithine (DMFO) | difluoromethylornithine | Iwilfin® | Ornidyl® | Vaniqa®
Approved drug
eflornithine is an approved drug (FDA (2000), EMA (2001))
Compound class: Synthetic organic
Comment: Eflornithine is an irreversible ornithine decarboxylase inhibitor [1,4] and is a partial inhibitor of arginase enzymes [6]. Marketed formulations may contain eflornithine hydrochloride (PubChem CID 57004).

Eflornithine has recently been reported to provide neuroprotective effects in a mouse model of Alzheimer's disease (AD) [3]. The authors identify microglial-induced arginine depletion as a causative factor in AD pathophysiology in their model, focussing on inhibition of arginine catabolising enzymes as a novel mechanism by which to halt the neurodegeneration observed in AD. These findings suggest that eflornithine could be used as a starting point for medicinal chemists to identify novel compounds with anti-arginase activity in humans.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 89.34
Molecular weight 182.09
XLogP -2.71
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES NCCCC(C(=O)O)(C(F)F)N
Isomeric SMILES NCCCC(C(=O)O)(C(F)F)N
InChI InChI=1S/C6H12F2N2O2/c7-4(8)6(10,5(11)12)2-1-3-9/h4H,1-3,9-10H2,(H,11,12)
InChI Key VLCYCQAOQCDTCN-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Abeloff MD, Slavik M, Luk GD, Griffin CA, Hermann J, Blanc O, Sjoerdsma A, Baylin SB. (1984)
Phase I trial and pharmacokinetic studies of alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis.
J Clin Oncol, 2 (2): 124-30. [PMID:6422008]
2. EMA. 
EU/3/16/1679.
Accessed on 23/01/2019. Modified on 23/01/2019. www.ema.europa.eu, https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3161679
3. Kan MJ, Lee JE, Wilson JG, Everhart AL, Brown CM, Hoofnagle AN, Jansen M, Vitek MP, Gunn MD, Colton CA. (2015)
Arginine deprivation and immune suppression in a mouse model of Alzheimer's disease.
J Neurosci, 35 (15): 5969-82. [PMID:25878270]
4. Pepin J, Milord F, Guern C, Schechter PJ. (1987)
Difluoromethylornithine for arseno-resistant Trypanosoma brucei gambiense sleeping sickness.
Lancet, 2 (8573): 1431-3. [PMID:2891995]
5. Qu N, Ignatenko NA, Yamauchi P, Stringer DE, Levenson C, Shannon P, Perrin S, Gerner EW. (2003)
Inhibition of human ornithine decarboxylase activity by enantiomers of difluoromethylornithine.
Biochem J, 375 (Pt 2): 465-70. [PMID:12859253]
6. Selamnia M, Mayeur C, Robert V, Blachier F. (1998)
Alpha-difluoromethylornithine (DFMO) as a potent arginase activity inhibitor in human colon carcinoma cells.
Biochem Pharmacol, 55 (8): 1241-5. [PMID:9719479]