Home Tools

H-89 dihydrochloride

Catalog No. T6250 CAS 130964-39-5

Synonyms: Protein kinase inhibitor H-89 dihydrochloride, H 89 2HCl, 5-Isoquinolinesulfonamide

H-89 dihydrochloride (5-Isoquinolinesulfonamide) is a potent inhibitor of protein kinase A (PKA; IC50: 0.14 μM, Ki: 48 nM).

All products from TargetMol are for Research Use Only. Not for Human or Veterinary or Therapeutic Use.

H-89 dihydrochloride, CAS 130964-39-5

Pack Size	Availability	Price/USD
5 mg	In stock	$ 33.00
10 mg	In stock	$ 53.00
25 mg	In stock	$ 108.00
50 mg	In stock	$ 213.00
100 mg	In stock	$ 363.00
200 mg	In stock	$ 538.00
500 mg	In stock	$ 857.00
1 mL * 10 mM (in DMSO)	In stock	$ 48.00

Bulk Inquiry

Select Batch

Purity: 100%

Purity: 99.4%

Purity: 98.38%

Purity: 98.22%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	H-89 dihydrochloride (5-Isoquinolinesulfonamide) is a potent inhibitor of protein kinase A (PKA; IC50: 0.14 μM, Ki: 48 nM).
Targets&IC50	S6K1:80 nM (cell free), PKA:48 nM (Ki, cell free)
In vitro	H-89 was shown to have a potent and selective inhibitory action against protein kinase A, with Ki of 0.048 microM. Pretreatment with H-89 led to a dose-dependent inhibition of the forskolin-induced protein phosphorylation, with no decrease in intracellular cyclic AMP levels in PC12D cells, and the NGF-induced protein phosphorylation was not inhibited. H-89 also significantly inhibited the forskolin-induced neurite outgrowth from PC12D cells. This inhibition also occurred when H-89 was added before the addition of dibutyryl cAMP. Pretreatment of PC12D cells with H-89 (30 microM) inhibited significantly cAMP-dependent histone IIb phosphorylation activity in cell lysates but did not affect other protein phosphorylation activity [1]. H-89 also inhibits S6K1, MSK1, ROCK-II, PKBα, and MAPKAP-K1b with IC50 values of 0.08, 0.12, 0.27, 2.6, and 2.8 μM, respectively [2]. In skinned EDL fibers of the rat, force responses to depolarization (by ion substitution) were inhibited only slightly by 10 microM H-89, a concentration more than sufficient to fully inhibit PKA. At 1-2 microM, H-89 significantly slowed the repriming rate in rat skinned fibers. With 100 microM H-89, the force response to depolarization by ion substitution was completely abolished. In intact single fibers of the flexor digitorum longus (FDB) muscle of the mouse, 1-3 microM H-89 had no noticeable effect on action-potential-mediated Ca2+ transients [3].
In vivo	Different doses of H-89 (0.05, 0.1, 0.2 mg/100g) were administered intraperitoneally (i.p.), 30 min before intravenous (i.v.) infusion of PTZ (0.5% w/v). Intraperitoneal administration of H-89 (0.2 mg/100g) significantly increased seizure latency and threshold in PTZ-treated animals. Pretreatment of animals with PTX (50 and 100 mg/kg) attenuated the anticonvulsant effect of H-89 (0.2 mg/100g) in PTZ-exposed animals. H-89 (0.05, 0.2 mg/100g) prevented the epileptogenic activity of bucladesine (300 nM) with a significant increase of seizure latency and seizure threshold [4]. Treatment with H89 (10 mg/kg, administered i.p.) significantly inhibited AHR in OVA-sensitized/challenged mice, whereas it had no effect on airway responses in control mice. Treatment with H89 decreased eosinophil numbers by 80%, neutrophil numbers by 64% and lymphocyte numbers by 74% without any effect on macrophage. In the moderate model, the cell infiltrate consisted of 39.3% eosinophils, 58.5% macrophages, 1.9% neutrophils, and 0.3% lymphocytes and was entirely inhibited by H89 [5].
Kinase Assay	All protein kinase activities were linear with respect to time in every incubation. Assays were performed either manually for 10 min at 30 °C in 50 μl incubations using [γ-32P]ATP or with a Biomek 2000 Laboratory Automation Workstation in a 96-well format for 40 min at ambient temperature in 25 μl incubations using [γ-33P]ATP. The concentrations of ATP and magnesium acetate were 0.1 mM and 10 mM respectively unless stated otherwise. This concentration of ATP is 5–10-fold higher than the Km for ATP of most of the protein kinases studied in the present paper, but lower than the normal intracellular concentration, which is in the millimolar range. All assays were initiated with MgATP. Manual assays were terminated by spotting aliquots of each incubation on to phosphocellulose paper, followed by immersion in 50 mM phosphoric acid. Robotic assays were terminated by the addition of 5 μl of 0.5 M phosphoric acid before spotting aliquots on to P30 filter mats. All papers were then washed four times in 50 mM phosphoric acid to remove ATP, once in acetone (manual incubations) or methanol (robotic incubations), and then dried and counted for radioactivity [2].
Cell Research	After 48 h in culture, PCl2D cells are cultured in a test medium containing 30 μM H-89 for 1 h and then exposed to a 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 [1].
Animal Research	H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide], di-HCl Salt) (10 mg/kg) suspended in 5% DMSO in saline was administered i.p. two hours before each OVA challenge (or two hours before the last OVA challenge). Control animals received equivalent volumes (200 μl) of 5% DMSO in saline [5].

Synonyms	Protein kinase inhibitor H-89 dihydrochloride, H 89 2HCl, 5-Isoquinolinesulfonamide
Molecular Weight	519.28
Formula	C20H20BrN3O2S·2HCl
CAS No.	130964-39-5

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

H2O: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 51.9 mg/mL (100 mM)

References and Literature

1. Chijiwa T, 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 Mar 25;265(9):5267-72. 2. Davies SP, et al. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105. 3. Blazev R, et al. Effects of the PKA inhibitor H-89 on excitation-contraction coupling in skinned and intact skeletal muscle fibres. J Muscle Res Cell Motil. 2001;22(3):277-86. 4. Hosseini-Zare MS, et al. Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice. Eur J Pharmacol. 2011 Nov 30;670(2-3):464-70. 5. Reber LL, et al. The AGC kinase inhibitor H89 attenuates airway inflammation in mouse models of asthma. PLoS One. 2012;7(11):e49512. 6. Liu M, Yang Y, Tan B, et al. Gαi and Gβγ subunits have opposing effects on dexmedetomidine-induced sedation[J]. European journal of pharmacology. 2018 Jul 15;831:28-37. 7. Xu C, Zhao W, Huang X, et al. TORC2/3-mediated DUSP1 upregulation is essential for human decidualization[J]. Reproduction. 2021, 1(aop). 8. Fu T, Chai B, Shi Y, et al. Fargesin inhibits melanin synthesis in murine malignant and immortalized melanocytes by regulating PKA/CREB and P38/MAPK signaling pathways[J]. Journal of Dermatological Science. 2019 Mar 28. pii: S0923-1811(19)30069-6.

Citations

1. Han J, Wang Y, Qiu Y, et al. Single-cell sequencing unveils key contributions of immune cell populations in cancer-associated adipose wasting. Cell Discovery. 2022, 8(1): 1-22. 2. Zhang, Hongyan, et al. Intracellular AGR2 transduces PGE2 stimuli to promote epithelial–mesenchymal transition and metastasis of colorectal cancer.. Cancer Letters. 2021 3. Pan H, Lin Y, Dou J, et al. Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis. Cell Proliferation. 2020, 53(9): e12868 4. Fu T, Chai B, Shi Y, et al. Fargesin inhibits melanin synthesis in murine malignant and immortalized melanocytes by regulating PKA/CREB and P38/MAPK signaling pathways. Journal of Dermatological Science. 2019 Mar 28. pii: S0923-1811(19)30069-6. 5. Xu C, Zhao W, Huang X, et al. TORC2/3-mediated DUSP1 upregulation is essential for human decidualization. Reproduction. 2021, 1(aop). 6. Liu M, Yang Y, Tan B, et al. Gαi and Gβγ subunits have opposing effects on dexmedetomidine-induced sedation. European Journal of Pharmacology. 2018 Jul 15;831:28-37 7. Meng Y, Li W, Hu C, et al.Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance.Food Science and Human Wellness.2023, 12(6): 2061-2072. 8. Zhao W, Xu C, Peng L, et al.cAMP/PKA signaling promotes AKT deactivation by reducing CIP2A expression, thereby facilitating decidualization.Molecular and Cellular Endocrinology.2023: 111946. 9. Shan G, Bi G, Zhao G, et al.Inhibition of PKA/CREB1 pathway confers sensitivity to ferroptosis in non-small cell lung cancer.Respiratory Research.2023, 24(1): 1-15. 10. Cui S, Suo N, Yang Y, et al.The aminosteroid U73122 promotes oligodendrocytes generation and myelin formation.Acta Pharmacologica Sinica.2023: 1-12.

11. Zheng N, Liu S, Chen J, et al.SARS-CoV-2 NSP2 as a Potential Delivery Vehicle for Proteins.Molecular Pharmaceutics.2024

See More... Hide

Related compound libraries

This product is contained In the following compound libraries：

Inhibitor Library Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library Neuronal Differentiation Compound Library Anti-COVID-19 Compound Library Metabolism Compound Library Antioxidant Compound Library Anti-Cancer Metabolism Compound Library Oxidation-Reduction Compound Library Anti-Breast Cancer Compound Library

Related Products

Related compounds with same targets

PKI (5-24) Acetate(99534-03-9 free base) LX7101 2-Aminopurine JAK1/2/3 Inhibitor 1 Ellagic acid CCT128930 Isopedicin OSIP-486823

Dose Conversion

You can also refer to dose conversion for different animals. More

In vivo Formulation Calculator (Clear solution)

Step One: Enter information below

Dosage

mg/kg

Average weight of animals

Dosing volume per animal

Number of animals

Step Two: Enter the in vivo formulation

% DMSO+

% +

% Tween 80+

% ddH₂O

%DMSO+

Calculate Reset

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL)，Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation：Take μL DMSO master liquid, next add μL PEG300， mix and clarify, next add μL Tween 80，mix and clarify, next add μL ddH₂O, mix and clarify.

Note:

Be sure to add the solvent(s) in order. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Calculator

Molarity Calculator

Dilution Calculator

Reconstitution Calculation

Molecular Weight Calculator

Mass

Concentration

Volume

Molecular Weight

Molarity Calculator allows you to calculate the

Mass of a compound required to prepare a solution of known volume and concentration
Volume of solution required to dissolve a compound of known mass to a desired concentration
Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of a molarity calculation using the molarity calculator
What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol?
Enter 197.13 into the Molecular Weight (MW) box
Enter 10 into the Concentration box and select the correct unit (millimolar)
Enter 10 into the Volume box and select the correct unit (milliliter)
Press calculate
The answer of 19.713 mg appears in the Mass box

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Calculator the dilution required to prepare a stock solution

Calculate the dilution required to prepare a stock solution
The dilution calculator is a useful tool which allows you to calculate how to dilute a stock solution of known concentration. Enter C1, C2 & V2 to calculate V1.

See Example

An example of a dilution calculation using the Tocris dilution calculator
What volume of a given 10 mM stock solution is required to make 20ml of a 50 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=50 μM, V2=20 ml and V1 is the unknown:
Enter 10 into the Concentration (start) box and select the correct unit (millimolar)
Enter 50 into the Concentration (final) box and select the correct unit (micromolar)
Enter 20 into the Volume (final) box and select the correct unit (milliliter)
Press calculate
The answer of 100 microliter (0.1 ml) appears in the Volume (start) box

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Calculate the volume of solvent required to reconstitute your vial.

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial.
Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

Molecule Formula

Molecular Weight g/mol

Enter the chemical formula of a compound to calculate its molar mass and elemental composition

Tip: Chemical formula is case sensitive: C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed n the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

bottom

Tech Support

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

H-89 dihydrochloride 130964-39-5 Autophagy MAPK PI3K/Akt/mTOR signaling Tyrosine Kinase/Adaptors PKA S6 Kinase Inhibitor inhibit H 89 Protein kinase inhibitor H-89 H 89 dihydrochloride Protein kinase A H89 Dihydrochloride H-89 Dihydrochloride Protein kinase inhibitor H-89 dihydrochloride Protein kinase inhibitor H-89 Dihydrochloride H89 dihydrochloride H89 H 89 Dihydrochloride H 89 2HCl H-89 5-Isoquinolinesulfonamide inhibitor

Products are chemical reagents for research use only and are not intended for human use. We do not sell to patients.