eflornithine   

GtoPdb Ligand ID: 5176

Synonyms: 2-(difluoromethyl)ornithine (DMFO) | difluoromethylornithine | Ornidyl® | Vaniqa®
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.
2D Structure
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Physico-chemical Properties
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
SMILES / InChI / InChIKey
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
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]