Lixazinone (hydrogensulfate)

Lixazinone (RS-82856) hydrogensulfate is a selective inhibitor of cGMP-inhibited phosphodiesterase (PDE3) with an IC₅₀ value of 22 nM. Lixazinone hydrogensulfate exhibits positive inotropic effects, afterload reduction and antithrombotic properties. Lixazinone hydrogensulfate increases cyclic adenosine monophosphate (cAMP) levels in human platelets, inhibits thrombin-induced aggregation of human platelets, and blocks the photolabeling of PDE3 active sites by [³²P]cGMP. Lixazinone hydrogensulfate can be used in the research of polycystic kidney disease and congestive heart failure^[1][2][3][4]. In Vitro:Lixazinone (0.5-1 μM; 5 min at 30 °C) hydrogensulfate potently and selectively inhibits human platelet PDE3, with 0.5 μM causing 97% inhibition of PDE3 activity and minimal effect on PDE2 activity at 1 μM^[1].
Lixazinone (1 μM; 1 min at 37 °C) hydrogensulfate increases [³H]cAMP levels in human platelets by 177%^[1].
Lixazinone (1 μM; 1 min at 37 °C pre-incubation) hydrogensulfate fully inhibits thrombin-induced aggregation in human platelets^[1].
Lixazinone hydrogensulfate (1 μM; 1 min at 37 °C) moderately increases [³H]cAMP levels in human platelets treated with 20 nM PGI₂^[1].
Lixazinone (300 nM; 15 min dark at 0°C, 15 min UV irradiation) hydrogensulfate inhibits photolabelling of the 115 kDa PDE III subunit in rat platelet lysate and rat heart homogenate^[2].
Lixazinone (10 μM; 60 min) hydrogensulfate increases intracellular cAMP levels by 22% in quiescent MDCK cells^[3].
Lixazinone (10 μM) hydrogensulfate activates PKA by 27% in transfected quiescent MDCK cells^[3].
Lixazinone (10 μM; 72 hrs) hydrogensulfate significantly stimulates mitogenesis in quiescent MDCK cells, as measured by [³H]-thymidine incorporation^[3].
Lixazinone (10 μM; 5 mins) hydrogensulfate significantly activates B-Raf kinase activity, with no effect on Raf-1 kinase activity, in quiescent MDCK cells^[3].
Lixazinone (10 μM; 1 hr) hydrogensulfate increases ERK kinase activity by 810% in quiescent MDCK cells^[3].
Lixazinone (10 μM; 4 hrs) hydrogensulfate stimulates cyclin D kinase activity by 83% and cyclin E kinase activity by 58% in quiescent MDCK cells^[3].
Lixazinone (10 μM; 8 hrs) hydrogensulfate does not significantly alter expression of p21 or p27 in quiescent MDCK cells^[3].
Lixazinone (10 μM; 24 hrs) hydrogensulfate potently inhibits mitogenesis in rat glomerular mesangial cells, as measured by [³H]-thymidine incorporation^[3].
Lixazinone (1 nM-10 μM) hydrogensulfate inhibits cAMP phosphodiesterase activity in total homogenates of cultured primary rat mesangial cells with an IC₅₀ of 2.85 nM, a potency that correlates with its suppression of mitogenesis^[4].