H-89

H-89
Names
Preferred IUPAC name
N-(2-{[(2E)-3-(4-Bromophenyl)prop-2-en-1-yl]amino}ethyl)isoquinoline-5-sulfonamide
Identifiers
3D model (JSmol)
Abbreviations H-89
H89
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.201.023 Edit this at Wikidata
EC Number
  • 675-767-3
UNII
  • InChI=1S/C20H20BrN3O2S/c21-18-8-6-16(7-9-18)3-2-11-22-13-14-24-27(25,26)20-5-1-4-17-15-23-12-10-19(17)20/h1-10,12,15,22,24H,11,13-14H2/b3-2+ X markN
    Key: ZKZXNDJNWUTGDK-NSCUHMNNSA-N X markN
  • InChI=1/C20H20BrN3O2S/c21-18-8-6-16(7-9-18)3-2-11-22-13-14-24-27(25,26)20-5-1-4-17-15-23-12-10-19(17)20/h1-10,12,15,22,24H,11,13-14H2/b3-2+
    Key: ZKZXNDJNWUTGDK-NSCUHMNNBL
  • c1cc2cnccc2c(c1)S(=O)(=O)NCCNC/C=C/c3ccc(cc3)Br
Properties
C20H20BrN3O2S
Molar mass 446.36 g·mol−1
Soluble to 25 mM
Solubility in other solvents up to 100 mM in DMSO
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Exposure may cause irritation to eyes, mucous membranes, upper respiratory tract, and skin.
GHS labelling:
GHS07: Exclamation mark
Warning
H302, H312, H315, H319, H332, H335
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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H-89 is a protein kinase inhibitor with greatest effect on protein kinase A (PKA). H-89, derived from H-8 (N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide), was initially believed to act specifically as an inhibitor of PKA, being 30 times more potent than H-8 at inhibiting PKA and 10 times less potent at inhibiting protein kinase G. It achieves this through competitive inhibition of the adenosine triphosphate (ATP) site on the PKA catalytic subunit. However, subsequent work has suggested a variety of additional effects such as inhibition of other protein kinases (IC50 values of 80, 120, 135, 270, 2600 and 2800 nM for S6K1, MSK1, PKA, ROCKII, PKBα and MAPKAP-K1b respectively), and direct inhibition of various potassium currents.

In addition to its use in studying mechanisms of cell signalling, H-89 has also been used experimentally in vivo. H-89 has been shown to increase the threshold and latency of pentylenetetrazol-induced seizures and decrease morphine withdrawal symptoms in mice.

References

  1. ↑ "C&L Inventory". echa.europa.eu.
  2. ↑ Marunaka, Yoshinori; Niisato, Naomi (2003). "H89, an inhibitor of protein kinase A (PKA), stimulates Na+ transport by translocating an epithelial Na+ channel (ENaC) in fetal rat alveolar type II epithelium". Biochemical Pharmacology. 66 (6): 1083–9. doi:10.1016/S0006-2952(03)00456-8. PMID 12963496.
  3. ↑ Hidaka, H.; Inagaki, M.; Kawamoto, S.; Sasaki, Y. (1984-10-09). "Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C". Biochemistry. 23 (21): 5036–5041. doi:10.1021/bi00316a032. ISSN 0006-2960. PMID 6238627.
  4. ↑ Chijiwa, T.; Mishima, A.; Hagiwara, M.; Sano, M.; Hayashi, K.; Inoue, T.; Naito, K.; Toshioka, T.; Hidaka, H. (1990-03-25). "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". The Journal of Biological Chemistry. 265 (9): 5267–5272. doi:10.1016/S0021-9258(19)34116-X. ISSN 0021-9258. PMID 2156866.
  5. ↑ Murray, A. J. (2008). "Pharmacological PKA Inhibition: All May Not Be What It Seems". Science Signaling. 1 (22): re4. doi:10.1126/scisignal.122re4. PMID 18523239.
  6. ↑ Lochner, A.; Moolman, J. A. (2006). "The Many Faces of H89: A Review". Cardiovascular Drug Reviews. 24 (3–4): 261–74. doi:10.1111/j.1527-3466.2006.00261.x. PMID 17214602.
  7. ↑ Pearman, Charles; Kent, William; Bracken, Nicolas; Hussain, Munir (August 2006). "H-89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes". British Journal of Pharmacology. 148 (8): 1091–1098. doi:10.1038/sj.bjp.0706810. ISSN 0007-1188. PMC 1752020. PMID 16799649.
  8. ↑ Hosseini-Zare, Mahshid Sadat; Salehi, Forouz; Seyedi, Seyedeh Yalda; Azami, Kian; Ghadiri, Tahereh; Mobasseri, Mohammad; Gholizadeh, Shervin; Beyer, Cordian; Sharifzadeh, Mohammad (2011). "Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice". European Journal of Pharmacology. 670 (2–3): 464–70. doi:10.1016/j.ejphar.2011.09.026. PMID 21946102.
  9. ↑ Seyedi, Seyedeh Y.; Salehi, Forouz; Payandemehr, Borna; Hossein, Sara; Hosseini-Zare, Mahshid S.; Nassireslami, Ehsan; Yazdi, Behnoosh B.; Sharifzadeh, Mohammad (2014). "Dual effect of cAMP agonist on ameliorative function of PKA inhibitor in morphine-dependent mice". Fundamental & Clinical Pharmacology. 28 (4): 445–54. doi:10.1111/fcp.12045. PMID 24033391. S2CID 36095599.