H-89 dihydrochloride

• CAT Number: I001184
• CAS Number: 130964-39-5
• Molecular Formula: C20H20BrN3O2S • 2HCl
• Molecular Weight: 519.3
• Purity: ≥95%
• Synonyms: (E)-N-(2-((3-(4-bromophenyl)allyl)amino)ethyl)isoquinoline-5-sulfonamide dihydrochloride
• Target: PKA
• Solubility: DMSO: ≥ 50 mg/mL
• Storage: 3 years -20C powder
• IC50: 48 nM [1]
• InChIKey: GELOGQJVGPIKAM-WTVBWJGASA-N

H 89 is a potent and selective inhibitor of cyclic AMP-dependent protein kinase (protein kinase A) with IC50 of 48 nM; weak inhibition on PKG, PKC, CK1, CK2 and others kinases.IC50 value: 48 nM [1]Target: PKA inhibitorin vitro: H-89 inhibits protein kinase A, in competitive fashion against ATP. To examine the role of protein kinase A in neurite outgrowth of PC12 cells, H-89 was applied along with nerve growth factor (NGF), forskolin, or dibutyryl cAMP. Pretreatment with H-89 led to a dose-dependent inhibition of the forskolin-induced protein phosphorylation, with no decrease in intracellular cyclic AMP levels in PC12D cells, and the NGF-induced protein phosphorylation was not not inhibited. H-89 also significantly inhibited the forskolin-induced neurite outgrowth from PC12D cells [1]. In intact single fibres of the flexor digitorum longus (FDB) muscle of the mouse, 1-3 microM H-89 had no noticeable effect on action-potential-mediated Ca2+ transients. Higher concentrations (4-10 microM) caused Ca2+ transient failure in fibres stimulated at 20 Hz in a manner indicative of action-potential failure. At 10-100 microM, H-89 also inhibited net Ca2+ uptake by the SR and affected the Ca2+-sensitivity of the contractile apparatus in rat skinned fibres [2].in vivo: Intraperitoneal administration of H-89 (0.2 mg/100g) significantly increased seizure latency and threshold in PTZ-treated animals. Pretreatment of animals with PTX (50 and 100 mg/kg) attenuated the anticonvulsant effect of H-89 (0.2 mg/100g) in PTZ-exposed animals. H-89 (0.05, 0.2 mg/100g) prevented the epileptogenic activity of bucladesine (300 nM) with significant increase of seizure latency and seizure threshold [3].

Reference

[1]. Chijiwa T, et al. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. J Biol Chem. 1990 Mar 25;265(9):5267-72.
[2]. Blazev R, et al. Effects of the PKA inhibitor H-89 on excitation-contraction coupling in skinned and intact skeletal muscle fibres. J Muscle Res Cell Motil. 2001;22(3):277-86.
[3]. Hosseini-Zare MS, et al. Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice. Eur J Pharmacol. 2011 Nov 30;670(2-3):464-70.