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
No information available.
Summary of Clinical Use
This drug is used topically to treat facial hirsutism (excessive hair growth) and by injection for African sleeping sickness (trypanosomiasis). The EMA granted eflornithine orphan designation in 2016 for the treament of glioma [2].
Mechanism Of Action and Pharmacodynamic Effects
Eflornithine irreversibly inhibits ornithine decarboxylase, an enzyme that catalyses the conversion of ornithine to putrescine, and plays an important role in cell division and proliferation in the hair follicle. In sleeping sickness it is believed eflornithine kills trypanosomes by inhibiting their ornithine decarboxylase enzyme, which in these organisms is required for cell division [4].
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