生物活性

• 描述PKA is a ubiquitous cellular kinase, also known as cAMP-dependent protein kinase, and it is well-established that plays an important role in regulating several functions of cell processes, including regulation of glycogen, sugar, and lipid metabolism^[1]. H-89, as a newly synthesized isoquinolinesulfonamide, is a ATP-competitive, potent inhibitor of protein kinase A (PKA)( IC50 = 48 nM), and has weak inhibition on several other kinases with IC50 of 80, 120, 135, 270, 2600 and 2800 nM for S6K1, MSK1, PKA, ROCKII, PKBα and MAPKAP-K1b, respectively^[2]. H-89 has since been used extensively for evaluation of the role of PKA in the heart, osteoblasts, hepatocytes, smooth muscle cells, neuronal tissue, epithelial cells, etc^[3]. PC12D cells pretreatment with H-89 led to a dose-dependent inhibition of the forskolin-induced neurite outgrowth and protein phosphorylation. In vivo experimental method, in skinned EDL fibres of the rat, H-89 dihydrochloride with 1-2 μM significantly slowed the repriming rate in rat skinned fibres. Moreover, rat brain ventricles following an injection with the PKA antagonist, H-89 dihydrochloride, the body temperature is increased further due to the inhibition of TRPV1 phosphorylation^[4].
• 作用机制H-89 inhibit the significant modulator role of the cAMP-PKA intracellular signaling pathway mainly acting as a selective and potent inhibitor of protein kinase A (PKA).
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
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  NCT02757820	Anesthesia	Phase 2 Phase 3	Unknown	August 2017	Egypt ... more >> Assiut university Pediatric hospital Recruiting Assiut, Assiut governorate, Egypt, 715715 Contact: Hala S Abdel-Ghaffar, MD    +2 01003812011    hallasaad@yahoo.com    Contact: Omer S Makram, MBBCH    +2 01064686191    omarmakram347@yahoo.com Collapse <<

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• 参考文献

• [1] Dolan S, Nolan AM. Biphasic modulation of nociceptive processing by the cyclic AMP-protein kinase A signalling pathway in sheep spinal cord. Neurosci Lett. 2001;309(3):157-60.

  [2] Chijiwa T, Mishima A, 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;265(9):5267-72.

  [3] Lochner A, Moolman JA. The many faces of H89: a review. Cardiovasc Drug Rev. 2006;24(3-4):261-74.

  [4] Bao D, Zhao W, et al. H89 dihydrochloride hydrate and calphostin C lower the body temperature through TRPV1. Mol Med Rep. 2018;17(1):1599-1608.