H-89 dihydrochloride

SKU: orb1300937

Description

H-89 dihydrochloride

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 130964-39-5
• MW: 519.28
• Purity: 99.40%
• Formula: C₂₀H₂₀BrN₃O₂S·2HCl
• SMILES: Cl.Cl.Brc1ccc(\C=C\CNCCNS(=O)(=O)c2cccc3cnccc23)cc1
• Target: Autophagy,PKA,S6 Kinase
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:104 mg/mL (200.28 mM);5% DMSO+95% Saline:3.16 mg/mL (6.09 mM)

Bioactivity

• Target IC50:
  S6K1:80 nM (cell free)|PKA:48 nM (Ki, cell free)
• In Vivo:
  Different doses of H-89 (0.05, 0.1, 0.2 mg/100g) were administered intraperitoneally (i.p.), 30 min before intravenous (i.v.) infusion of PTZ (0.5% w/v). 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) attenuate the anticonvulsant effect of H-89 (0.2 mg/100g) in PTZ-exposed animals. H-89 (0.05, 0.2 mg/100g) prevente the epileptogenic activity of bucladesine (300 nM) with a significant increase of seizure latency and seizure threshold . Treatment with H89 (10 mg/kg, administered i.p.) significantly inhibited AHR in OVA-sensitized/challenged mice, whereas it had no effect on airway responses in control mice. Treatment with H89 decreased eosinophil numbers by 80%, neutrophil numbers by 64% and lymphocyte numbers by 74% without any effect on macrophage. in the moderate model the cell infiltrate consisted of 39.3% eosinophils, 58.5% macrophages, 1.9% neutrophils, and 0.3% lymphocytes and was entirely inhibited by H89.
• In Vitro:
  H-89 was shown to have a potent and Selective inhibitory action against protein kinase A, with Ki of 0.048 microM. Pretreatment with H-89 led to a dose-dependent Inhibition o the forskolin-induced protein phosphorylation, with no decrease in intracellular cyclic AMP levels in PC12D cells, an the NGF-induced protein phosphorylation was not inhibited. H-89 also significantly inhibite the forskolin-induced neurite outgrowth from PC12D cells. This Inhibition also occurred when H-89 was added befor the addition of dibutyryl cAMP. Pretreatment of PC12D cells with H-89 (30 microM) inhibited significantly cAMP-dependent histone IIb phosphorylation activity in cell lysates but did not affect Other protein phosphorylation activity. H-89 also inhibits S6K1, MSK1, ROCK-II, PKBα, and MAPKAP-K1b with IC50 Values of 0.08, 0.12, 0.27, 2.6, and 2.8 μM, respectively. In skinned EDL fibers o the rat, force responses to depolarization (by ion substitution) were inhibited only slightly by 10 microM H-89, a concentration more than sufficient to fully inhibit PKA. At 1-2 microM, H-89 significantly slowe the repriming rate in rat skinned fibers. With 100 microM H-89 the force response to depolarization by ion substitution was completely abolished. In intact Single fibers o the flexor digitorum longus (FDB) musclee o the mouse, 1-3 microM H-89 had no noticeable effect on action-potential-mediated Ca2+ transients.
• Cell Research:
  After 48 h in culture, PCl2D cells are cultured in a test medium containing 30 μM H-89 for 1 h and then exposed to a fresh medium that contained both 10 μM forskolin and 30 μM H-89. Cells are scraped off with a rubber policeman and sonicated in the presence of 0.5 mL of 6% trichloroacetic acid. To extract trichloroacetic acid, 2 ml of petroleum ether is added the preparation mixed and centrifuged at 3000 rpm for 10 min. After aspiration o the upper layer the residue sample solution is used for determination.
• Animal Research:
  H89 (N [2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide], di-HCl Salt) (10 mg/kg) suspended in 5% DMSO in saline was administered i.p. Two hours before Each OVA challenge (or two hours befor the last OVA challenge). Control animals received equivalent volumes (200 μL) of 5% DMSO in saline.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Autophagy, H89, H-89, H-89 Dihydrochloride, H 89, H 89 2HCl, PKA, Protein kinase inhibitor H-89, Protein kinase inhibitor H-89 dihydrochloride, S6Kinase, S6K1, S6 Kinase

Compound Identifiers

PubChem CID

5702541