EHNA HCl | PDE2 inhibitor

EHNA (51350-19-7) inhibits phosphodiesterase 2 (PDE2) (IC₅₀ = 0.8 – 5.5 µM in a variety of tissues and species) over PDE1, PDE3, or PDE4 (IC₅₀ values > 100 µM).^1,2 It also inhibits adenosine deaminase (ADA), IC₅₀ = 1.2 and 1.5 µM in human RBCs and astrocytoma cells, respectively³, which may be responsible for its ability to induce apoptosis in malignant pleural mesothelioma cell lines⁴. Because it blocks breakdown of adenosine to inosine and hypoxanthine, EHNA prevents formation of free radical substrates, protecting against cardiac reperfusion-mediated injury.⁵ It inhibits differentiation and maintains expression of pluripotency markers in hESCs, but not through inhibition of PDEs or ADA.⁶

References:

1. Podzuweit et al. (1995), Isoenzyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythron-9-(2-hydroxy-3-nonyl) adenine; Cell Signal., 7 733
2. Méry et al. (1995), Erythro-9-(2-hydroxy-3-nonyl)adenine inhibits cyclic GMP-stimulated phosphodiesterase in isolated cardiac myocytes; Mol. Pharmacol., 48 121
3. Barankiewicz et al. (1997), Regulation of adenosine concentration and cytoprotective effects of novel reversible adenosine deaminase inhibitors; J. Pharmacol. Exp. Ther., 283 1230
4. Nakajima et al. (2015), Adenosine deaminase inhibitor EHNA exhibits a potent anticancer effect against malignant pleural mesothelioma; Cell Physiol. Biochem., 35 51
5. Abd-Elfattah and Wechsler (1994), Separation between ischemic and reperfusion injury by site specific entrapment of endogenous adenosine and inosine using NBMPR and EHNA; Card. Surg., 9 387
6. Burton et al. (2010), Erythro-9-(2-hydroxy-3-nonyl)adenine(EHNA) blocks differentiation and maintains the expression of pluripotency markers in human embryonic stem cells; Biochem. J., 432 575