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
CAS Number	127243-85-0 ;
3D model (JSmol)	Interactive image;
Abbreviations	H-89; H89
ChEBI	CHEBI:47495 ;
ChEMBL	ChEMBL104264 ;
ChemSpider	395827 ;
DrugBank	DB07995;
ECHA InfoCard	100.201.023
EC Number	675-767-3;
IUPHAR/BPS	5983;
PubChem CID	449241;
UNII	M876330O56 ;
	InChI 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+ Key: ZKZXNDJNWUTGDK-NSCUHMNNSA-N ; 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;
	SMILES c1cc2cnccc2c(c1)S(=O)(=O)NCCNC/C=C/c3ccc(cc3)Br;
Properties
Chemical formula	C20H20BrN3O2S
Molar mass	446.36 g·mol−1
Solubility in water	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:
Pictograms
Signal word	Warning
Hazard statements	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). verify (what is ?) Infobox references

H-89 is a protein kinase inhibitor with greatest effect on protein kinase A (PKA).^[2] H-89, derived from H-8 (N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide),^[3] was initially believed to act specifically as an inhibitor of PKA,^[4] 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.^[5] 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),^[6] and direct inhibition of various potassium currents.^[7]

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 ^[8] and decrease morphine withdrawal symptoms in mice.^[9]

References[edit]

^ "C&L Inventory". echa.europa.eu.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

[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.

[example_web_reference-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.

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