A potent inhibitor of iNOS and nNOS
1,4-PBIT (dihydrobromide) is a potent inhibitor of iNOS and nNOS with Ki values of 7.4 and 16 nM, respectively [1].
Nitric oxide (NO) is an endogenously produced inorganic free radical gas which has been implicated in blood pressure homeostasis, platelet aggregation, neurotransmission, and immunological defense mechanisms. NO is synthesized by three isoforms of nitric oxide synthase (NOS): nNOS, eNOS and iNOS [1].
1,4-PBIT, also known as S,S’-(1,4-Phenylenebis(1,2-ethanediyl))bisisothiourea, is a potent and selective iNOS and nNOS inhibitor. 1,4-PBIT inhibited purified human iNOS, eNOS and nNOS with Ki values of 7.4 nM, 360 nM and 16 nM, respectively. In DLD-1 cells, 1,4-PBIT inhibited human iNOS with IC50 value of 30 μM, presumably to poor membrane permeability [1].
In anesthetized rats, 1,4-PBIT (10 mg/kg, given 1 h after LPS administration), 1,4-PBIT effectively reversed the systemic hypotension, reduced the exhaled NO concentration and prevented acute lung injury. 1,4-PBIT also significantly depressed LPS-induced mRNA expressions of iNOS and IL-1β[2].
参考文献:
[1].? Garvey EP, Oplinger JA, Tanoury GJ, et al. Potent and selective inhibition of human nitric oxide synthases. Inhibition by non-amino acid isothioureas. J Biol Chem. 1994 Oct 28;269(43):26669-76.
[2].? Wang D, Wei J, Hsu K, et al. Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats. J Biomed Sci. 1999 Jan;6(1):28-35.
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