L-Ornithine, N5-[(1,1-dimethylethoxy)carbonyl]-N2-[[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinyl]methyl]-, methyl ester

Description

POB (946135-39-3) is a transition state-based, cell permeable pro-drug inhibitor of ODC, a key enzyme involved in polyamine synthesis and a potential cancer drug target. Intracellularly, POB is phosphorylated by pyridoxal kinase and the methyl ester hydrolyzed. This active inhibitor most likely binds apo-ODC resulting in greatly reduced ODC activity and inhibition of cellular proliferation. POB was able to inhibit proliferation in a wide variety of tumor cell lines: LN229 (IC50?= 50 μM), Jurkat, COS7, SW2 and both high and low-grade glioblastoma multiforme. More potent than DFMO.

Uses

POB is the best known reversible inhibitor of ornithine decarboxylase (ODC), a key enzyme involved in polyamine synthesis and a potential cancer drug target. POB is efficient in inhibiting proliferation of several types of tumor cells.

References

1) Wu?et al. (2007),?New transition state-based inhibitor for human ornithine decarboxylase inhibits growth of tumor cells; Mol. Cancer Ther.,?6?1831 2) Wu?et al. (2011),?A novel approach to inhibit intracellular vitamin B6-dependent enzymes: proof of principle with human and plasmodium ornithine decarboxylase and human histidine decarboxylase; FASEB J.,?25?2109