H-89 is a

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...

inhibitor with greatest effect on

protein kinase A In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulatio ...

(PKA). H-89, derived from H-8 (N-

-(methylamino)ethyl The hyphen-minus is the most commonly used type of hyphen, widely used in digital documents. It is the only character that looks like a minus sign or a dash in many character sets such as ASCII or on most keyboards, so it is also used as such. ...

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 cGMP-dependent protein kinase or protein kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle ...

. It achieves this through competitive inhibition of the

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...

(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 Ribosomal protein S6 kinase beta-1 (S6K1), also known as p70S6 kinase (p70S6K, p70-S6K), is an enzyme (specifically, a protein kinase) that in humans is encoded by the ''RPS6KB1'' gene. It is a serine/threonine kinase that acts downstream of PIP3 ...

, MSK1,

PKA PKA may refer to: * Professionally known as: ** Pen name ** Stage persona * p''K''a, the symbol for the acid dissociation constant at logarithmic scale * Protein kinase A, a class of cAMP-dependent enzymes * Pi Kappa Alpha, the North-American so ...

, 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 Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

''. H-89 has been shown to increase the threshold and latency of pentylenetetrazol-induced seizures and decrease morphine withdrawal symptoms in mice.

References

{{reflist Isoquinolines Organobromides Sulfonamides Protein kinase inhibitors