2,4-DPD

The pro-angiogenic factor HIF-1α is targeted for destruction in normoxic environments by the hydroxylation of a specific proline residue, P564, by the oxygen-sensing enzyme HIF-α prolyl hydroxylase (HIF-PH).¹ 2,4-DPD is a cell permeable, competitive inhibitor of HIF-PH. 2,4-DPD inhibits the hydroxylation of P564 by acting as a competitive inhibitor of the HIF-PH cofactor α-keto glutarate, with effective concentrations in the low µM range.² 2,4-DPD is therefore expected to act as a pro-angiogenic compound, via the HIF-1α system.^3,4

WARNING This product is not for human or veterinary use.

1. Jaakkola, P., Mole, D.R., Tian, Y.M., et al. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O₂-regulated prolyl hydroxylation. Science 292(5516), 468-472 (2001).

2. Friedman, L., Higgin, J.J., Moulder, G., et al. Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 97(9), 4736-4741 (2000).

3. Bruick, R., and McKnight, S.L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294(5545), 1337-1340 (2001).

4. Ivan, M., Kondo, K., Yang, H., et al. HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O₂ sensing. Science 292(5516), 464-468 (2001).