D-Eflornithine (monohydrochloride)

D-Eflornithine monohydrochloride is an enantiomer of Eflornithine. D-Eflornithine is an irreversible ornithine decarboxylase (ODC) inhibitor with a K_D of 28.3±3.4 µM, and a K_inact of 0.25±0.03 min^-1[1]. IC50 & Target: KD: 28.3±3.4 µM (Ornithine decarboxylase, ODC)^[1] In Vitro: 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 (K_D) 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 (K_inact) 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. D-Eflornithine (D-DFMO) is a more potent inhibitor (IC50 ~7.5 µM) when compared with D-ornithine (IC50 ~1.5 mM) of ODC-catalysed L-ornithine decarboxylation^[1].
D-Eflornithine has some advantages, such as decreases normal tissue toxicity, over L-Eflornithine or Eflornithine^[1].
In Vivo: L-Eflornithine displays a relatively lower bioavailability (30%) than that of the D-Eflornithine (59%). 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].