H 89 2HCl 130964-39-5

Molecular Weight: 519.28 H 89 2HCl is a potent PKA Inhibitor with Ki of 48 nM, 10-fold selective for PKA than PKG, greater than 500-fold selectivity than PKC, MLCK, calmodulin kinase II and casein kinase I/II.


Biological Activity


H89 2HCl is a potent PKA (cAMP-dependent) protein kinase A inhibitor with Ki of 48 nM, exhibits 10-fold selectivity over PKG, exhibits >500-fold
selectivity over PKC, MLCK, calmodulin kinase II and casein kinase I/II.
Pretreatment of the cells with H-89 (30 μM) 1 h before the addition of
forskolin markedly inhibits the forskolin-induced protein
phosphorylation in a dose-dependent manner. H89 also
inhibits several other kinases with IC50 of 80, 120, 135, 270, 2600 and
2800 nM for S6K1, MSK1, PKA, ROCKII, PKBα and MAPKAP-K1b, respectively. H89 also has activity at some cellular receptors and ion channels, including Kv1.3 K+ channels,β1AR and β2AR.


H89 causes distinct modifications of protein phosphorylation, with the
most robust changes in phosphorylation are fructose-1,6-biphosphatase,
heterogeneous nuclear ribonucleoprotein (hnRNP), NSFL1 cofactor p47, all
which have potentially regulatory connections to cAMP/PKA.


Protocol(Only for Reference)


Kinase Assay: [1]

PKA enzyme activity	cAMP-dependent protein kinase activity is assayed in a reaction mixture containing, in a final volume of 0.2 mL, 50 mM Tris-HC1 (pH 7.0), 10 mM magnesium acetate, 2 mM EGTA, 1 μM cAMP or absence of cAMP, 3.3-20 μM [γ-32P]ATP (4 × 105 cpm), 0.5 μg of the enzyme, 100 μg of histone H2B, and each compound, as indicated.

Cell Assay: [1]

Cell lines	PC12D
Concentrations	~30 μM
Incubation Time	1 h
Method	Levels of intracellular cAMP are determined. After 48 h in culture, PC12D cells are cultured in test medium containing 30 μM H-89 for 1 h and then exposed to fresh medium that contained both 10 μM forskolin and 30 μM H-89. Cells are scraped off with a rubber policeman and sonicated in the presence of 0.5 ml of 6% trichloroacetic acid. To extract trichloroacetic acid, 2 ml of petroleum ether is added, the preparation mixed and centrifuged at 3000 rpm for 10 min. After aspiration of the upper layer, the residue sample solution is used for determination.

Animal Study: [5][6]

Animal Models	rat; mice
Formulation	Dissolved in 100% DMSO, diluted 1:20 in 0.9% sterile saline (Rat); 1% DMSO (Mice)
Dosages	20 or 200 mg/kg (Rat); 0-5 mg/kg (Mice)
Administration	s.c. (Rat); i.p. (Mice)
Solubility	1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

Chemical Information

Molecular Weight (MW)	519.28
Formula	C20H20BrN3O2S.2HCl
CAS No.	130964-39-5

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms

Solubility (25°C) *	In vitro	DMSO	104 mg/mL (200.27 mM)
		Water	6 mg/mL (11.55 mM)
		Ethanol	<1 mg/mL (
	In vivo	1% DMSO/30% polyethylene glycol/1% Tween 80	30 mg/mL

Chemical Name	(E)-N-(2-(4-bromocinnamylamino)ethyl)isoquinoline-5-sulfonamide dihydrochloride

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