L-DABA

L-DABA (L-2,4-Diaminobutyric acid) is a week GABA transaminase inhibitor with an IC₅₀ of larger than 500 μM; exhibits antitumor activity in vivo and in vitro. IC50 & Target: IC50: larger than 500 μM (GABA transaminase)^[1] In Vitro: The tumor cells are irreversibly and totally damaged by incubation with 10 mM L-2,4-Diaminobutyric acid for 24 h at 37°C. The cell-destructive effect by L-DABA is probably due to an osmotic lysis induced by the non-saturated intracellular accumulation of L-DABA. The harmful effect of L-DABA could be abolished by concomitant incubation with L-alanine and L-methionine^[1]. Kinetic studies indicates that L-DABA is a non-linear, non-competitive inhibitor of GABA transaminase activity. The L-DABA-induced elevation of GABA levels parallels the inhibition of GABA transaminase activity^[2]. L-2,4-Diaminobutyric acid, an amino acid analogue, produceS a cytolytic effect with a human glioma cell line, SKMG-1, and normal human fibroblasts. The concentrations of L-DABA necessary to reduce the cell count to 50% of control following a 24-h incubation at 37°C are 12.5 mM for the human fibroblasts and 20 mM for the glioma cell line^[3]. In Vivo: Treatment with L-DABA results in 43.4% reduction of tumor growth^[1]. L-DABA is a more effective inhibitor of GABA transaminase in vivo than in vitro^[2].