HET0016 | 20-HETE biosynthesis inhibitor

HET0016 (339068-25-6) inhibits 20-hydroxyeicosatetraenoic acid (20-HETE) biosynthesis via omega oxidation of arachidonic acid mediated by CYP4A and 4F (IC₅₀=8.9 nM in human renal microsomes).¹ It displays neuroprotective effects in a rat model of traumatic brain injury via inhibition of neuronal pyroptosis.² HET0016 attenuates cerebral ischemia-reperfusion injury³ as well as oxidative injury and peripheral nerve damage in type-2 diabetic mice⁴. It alleviates myocardial oxidative stress⁵ and restores endothelial function suggesting therapeutic potential in obesity-associated vascular disease⁶.

References/Citations:

1. Miyata et al. (2001), HET0016, a potent and selective inhibitor of 20-HETE synthesizing enzyme; Br. J. Pharmacol. 133 325
2. Chen et al. (2023), HET0016 inhibits neuronal pyroptosis in the immature brain post-TBI via the p38 MAPK signaling pathway; Neuropharmacology, 239 109687
3. Yang et al. (2020), N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine attenuates oxygen-glucose deprivation and reoxygenation-induced cerebral ischemia-reperfusion injury via regulation of microRNAs; J. Integr. Neuroscience 19 303
4. Haddad et al. (2022), Activation of 20-HETE Synthase Triggers Oxidative Injury and Peripheral Nerve Damage in Type 2 Diabetic Mice; J. Pain 23 1371
5. Wang et al. (2019), Specific Inhibition of CYP4A Alleviates Myocardial Oxidative Stress and Apoptosis Induced by Advanced Glycation End-Products; Front. Pharmacol. 10 876
6. Munoz et al. (2022), Differential contribution of renal cytochrome P450 enzymes to kidney endothelial dysfunction and vascular oxidative stress in obesity; Biochem. Pharmacol. 195 114850