2,4-Pyridinedicarboxylic Acid (hydrate)

2,4-Pyridinedicarboxylic Acid (2,4-PDCA) is a compound that structurally mimics 2-oxoglutarate (2-OG, also known as α-ketoglutarate) and chelates zinc, thus affecting a range of enzymes.^1,2 As a 2-OG mimic, it blocks the activity of 2-OG oxygenases, which include certain lysine demethylases and a variety of hydroxylases (e.g., prolyl, collagen, lysyl).^2,3 2,4-PDCA inhibits several Jumonji domain-containing lysine demethylases when used at low micromolar concentrations.^4,5,6 Through its effects on hydroxylases, including prolyl hydroxlase 1 (IC₅₀ = 1.5 µM), 2,4-PDCA modulates hypoxia-inducible factor turnover, collagen synthesis, and plant cell wall formation.^2,7 It can inhibit zinc-dependent enzymes, like metallo-β-lactamase.⁸ 2,4-PDCA also affects and is translocated by organic anion transporters.⁹

WARNING This product is not for human or veterinary use.

1. Kidani, Y., and Hirose, J. Coordination chemical studies on metalloenzymes II. Kinetic behavior of various types of chelating agents towards bovine carbonic anhydrase. J. Biochem. 81(5), 1383-1391 (1977).

2. Koski, M.K., Hieta, R., Böllner, C., et al. The active site of an algal prolyl 4-hydroxylase has a large structural plasticity. The Journal of Biological Chemisty 282(51), 37112-37123 (2007).

3. Mackeen, M.M., Kramer, H.B., Chang, K.H., et al. Small-molecule-based inhibition of histone demethylation in cells assessed by quantitative mass spectrometry. J. Proteome Res. 9(8), 4082-4092 (2010).

4. Leurs, U., Clausen, R.P., Kristensen, J.L., et al. Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C). Bioorg. Med. Chem. Lett. 22(18), 5811-5813 (2012).

5. King, O.N.F., Li, X.S., Sakurai, M., et al. Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors. PLoS One 5(11), 1-12 (2010).

6. Kristensen, L.H., Nielsen, A.L., Helgstrand, C., et al. Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor. FEBS J. 279(11), 1905-1914 (2012).

7. Hamada, S., Suzuki, T., Mino, K., et al. Design, synthesis, enzyme-inhibitory activity, and effect on human cancer cells of a novel series of Jumonji domain-containing protein 2 histone demethylase inhibitors. J. Med. Chem. 53(15), 5629-5638 (2010).

8. Horsfall, L.E., Garau, G., Liénard, B.M.R., et al. Competitive inhibitors of the CphA metallo-β-lactamase from Aeromonas hydrophila. Antimicrob. Agents Chemother. 51(6), 2136-2142 (2007).

9. Hagos, Y., Schley, G., Schödel, J., et al. α-Ketoglutarate-related inhibitors of HIF prolyl hydroxylases are substrates of renal organic anion transporters 1 (OAT1) and 4 (OAT4). Pflugers Arch. 464(4), 367-374 (2012).