L-Eflornithine monohydrochloride

• CAT Number: I019649
• CAS Number: 69955-42-6
• Molecular Formula: C6H13ClF2N2O2
• Molecular Weight: 218.63
• Purity: ≥95%
• Synonyms: (2S)-2,5-diamino-2-(difluoromethyl)pentanoic acid;hydrochloride
• InChI: InChI=1S/C6H12F2N2O2.ClH/c7-4(8)6(10,5(11)12)2-1-3-9;/h4H,1-3,9-10H2,(H,11,12);1H/t6-;/m1./s1
• InChIKey: VKDGNNYJFSHYKD-FYZOBXCZSA-N
• SMILES: C(CC(C(F)F)(C(=O)O)N)CN.Cl

L-Eflornithine monohydrochloride (L-DFMO monohydrochloride) is an enantiomer of Eflornithine. L-Eflornithine is an irreversible ornithine decarboxylase (ODC) inhibitor with a KD of 1.3±0.3 µM, and a Kinact of 0.15±0.03 min-1[1].
Eflornithine (D/L-DFMO) is an inhibitor of ODC, the first enzyme in eukaryotic polyamine biosynthesis. Both enantiomers of Eflornithine (DFMO) irreversibly inactivate ODC. Both Eflornithine enantiomers (L-Eflornithine and D-Eflornithine) suppress ODC activity in a time- and concentration-dependent manner. The inhibitor dissociation constant (KD) values for the formation of enzyme-inhibitor complexes are 28.3±3.4, 1.3±0.3 and 2.2±0.4 µM respectively for D-Eflornithine, L-Eflornithine and Eflornithine. The inhibitor inactivation constants (Kinact) for the irreversible step were 0.25±0.03, 0.15±0.03 and 0.15±0.03 min-1 respectively for D-Eflornithine, L-Eflornithine and Eflornithine. Treatment of human colon tumour-derived HCT116 cells with either L-Eflornithine or D- Eflornithine decreases the cellular polyamine contents in a concentration-dependent manner[1]. The enantiomers display different potencies in vitro, with the L-enantiomer having up to a 20-fold higher affinity for the target enzyme ornithine decarboxylase[2].
The L-Eflornithine also appears to be more potent in cultured T.brucei gambiense parasites[2].
The more potent L-Eflornithine is present at much lower concentrations in both plasma and cerebrospinal fluid (CSF) than those of the D-Eflornithine. The plasma concentrations of L-Eflornithine are on average 52% of the D-enantiomer concentrations. The typical oral clearances of L-Eflornithine and D-eflornithine are 17.4 and 8.23 liters/h, respectively[2].

Reference

[1]. Qu N, et al. Inhibition of human ornithine decarboxylase activity by enantiomers of difluoromethylornithine. Biochem J. 2003 Oct 15;375(Pt 2):465-70.
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[2]. Jansson-Löfmark R, et al. Enantiospecific reassessment of the pharmacokinetics and pharmacodynamics of oral eflornithine against late-stage Trypanosoma brucei gambiense sleeping sickness. Antimicrob Agents Chemother. 2015 Feb;59(2):1299-307.
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