Description
The H series isoquinolinesulfonamide protein kinase (PK) inhibitors are widely used to block signaling pathways to elucidate mechanisms of cellular regulation and signal transduction. H-
8, an isoquinolinesulfonamide protein kinase (PK) inhibitor, is a potent inhibitor of PKA and PKG and shows moderate inhibition for PKC and MLCK with K
i values of 1.2, 0.48, 15, and 68 μM, respectively. H-
8 can disrupt transcriptional elongation by inhibiting cyclin C/Cdk8 and cyclin H/Cdk7/p36 CTD kinase activity with IC
50 values of 47 and 6.2 μM, respectively.
Chemical Properties
white to off-white crystalline solid
Uses
Active inhibitor of cyclic-nucleotide-dependent protein kinases.
Biochem/physiol Actions
cAMP and cGMP-dependent protein kinase inhibitor.
References
[1] R A ENGH. Crystal structures of catalytic subunit of cAMP-dependent protein kinase in complex with isoquinolinesulfonyl protein kinase inhibitors H7, H8, and H89. Structural implications for selectivity.[J]. The Journal of Biological Chemistry, 1996, 271 42: 26157-26164. DOI:
10.1074/jbc.271.42.26157[2] HIROYOSHI HIDAKA. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide-dependent protein kinase and protein kinase C[J]. Biochemistry Biochemistry, 1984, 23 21: 5036-5041. DOI:
10.1021/bi00316a032[3] M HAGIWARA H H M Inagaki. Specific binding of a novel compound, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) to the active site of cAMP-dependent protein kinase.[J]. Molecular Pharmacology, 1987, 31 5: 523-528.
[4] P RICKERT E L J L Corden. Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases.[J]. Oncogene, 1999, 18 4: 1093-1102. DOI:
10.1038/sj.onc.1202399
