H-89 (dihydrochloride)

H-89 dihydrochloride is a potent and selective inhibitor of protein kinase A (PKA) with an IC₅₀ of 48 nM and has weak inhibition on PKG, PKC, Casein Kinase. IC50 & Target: IC50: 48 nM (protein kinase A) In Vitro: H-89 inhibits protein kinase A, in competitive fashion against ATP. H-89 causes a dose-dependent inhibition of the forskolin-induced protein phosphorylation, with no decrease in intracellular cyclic AMP levels in PC12D cells. H-89 significantly inhibits the forskolin-induced neurite outgrowth from PC12D cells. H-89 (30 μM) inhibits significantly cAMP-dependent histone IIb phosphorylation activity in PC12D cell lysates^[1]. H-89 (1-2 μM) significantly slows the repriming rate in rat skinned fibres, most likely due to it deleteriously affecting the T-system potential. H-89 (10-100 μM) inhibits net Ca²⁺ uptake by the SR and affectes the Ca²⁺-sensitivity of the contractile apparatus in rat skinned fibres^[2]. In Vivo: H-89 (0.2 mg/100g, i.p.) significantly increases seizure latency and threshold in PTZ-treated animals. H-89 (0.05, 0.2 mg/100 g, i.p.) prevents the epileptogenic activity of bucladesine (300 nM) with significant increase of seizure latency and seizure threshold^[3].