HET0016, a potent and selective inhibitor of 20‐HETE synthesizing enzyme | Zendy

Miyata Noriyuki | Zendy; Taniguchi Kazuo | Zendy; Seki Takayuki | Zendy; Ishimoto Tsuyoshi | Zendy; SatoWatanabe Mariko | Zendy; Yasuda Yoshiko | Zendy; Doi Mariko | Zendy; Kametani Shunichi | Zendy; Tomishima Yasumitsu | Zendy; Ueki Tomokazu | Zendy; Sato Masakazu | Zendy; Kameo Kazuya | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Premium

HET0016, a potent and selective inhibitor of 20‐HETE synthesizing enzyme

Author(s) -

Miyata Noriyuki,

Taniguchi Kazuo,

Seki Takayuki,

Ishimoto Tsuyoshi,

SatoWatanabe Mariko,

Yasuda Yoshiko,

Doi Mariko,

Kametani Shunichi,

Tomishima Yasumitsu,

Ueki Tomokazu,

Sato Masakazu,

Kameo Kazuya

Publication year - 2001

Publication title -

british journal of pharmacology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.432

H-Index - 211

eISSN - 1476-5381

pISSN - 0007-1188

DOI - 10.1038/sj.bjp.0704101

Subject(s) - microsome , enzyme , arachidonic acid , cytochrome p450 , chemistry , metabolism , cyp3a4 , biochemistry , enzyme kinetics , active site

The present study examined the inhibitory effects of N‐Hydroxy‐N′‐(4‐butyl‐2‐methylphenyl)‐formamidine (HET0016) on the renal metabolism of arachidonic acid by cytochrome P450 (CYP) enzymes. HET0016 exhibited a high degree of selectivity in inhibiting the formation of 20‐hydroxy‐5,8,11,14‐eicosatetraenoic acid (20‐HETE) in rat renal microsomes. The IC 50 value averaged 35±4 n M , whereas the IC 50 value for inhibition of the formation of epoxyeicosatrienoic acids by HET0016 averaged 2800±300 n M . In human renal microsomes, HET0016 potently inhibited the formation of 20‐HETE with an IC 50 value of 8.9±2.7 n M . Higher concentrations of HET0016 also inhibited the CYP2C9, CYP2D6 and CYP3A4‐catalysed substrates oxidation with IC 50 values of 3300, 83,900 and 71,000 n M . The IC 50 value for HET0016 on cyclo‐oxygenase activity was 2300 n M . These results indicate that HET0016 is a potent and selective inhibitor of CYP enzymes responsible for the formation of 20‐HETE in man and rat. British Journal of Pharmacology (2001) 133 , 325–329; doi: 10.1038/sj.bjp.0704101

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here

Accelerating Research