H-89 free base | CAS#127243-85-0 | Protein kinase A inhibitor

MedKoo Cat#: 530546 | Name: H-89 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

H-89 is a specific adenylyl cyclase inhibitor (DDA) and a cyclic AMP-dependent protein kinase inhibitor. H-89 blocks the action of equine growth hormone on in vitro maturation of equine oocytes. H-89 decreases the gain of excitation-contraction coupling and attenuates calcium sparks in the absence of beta-adrenergic stimulation. H-89 potentiates adipogenesis in 3T3-L1 cells by activating insulin signaling independently of protein kinase A.

Chemical Structure

H-89 free base

CAS#127243-85-0 (free base)

Theoretical Analysis

MedKoo Cat#: 530546

Name: H-89 free base

CAS#: 127243-85-0 (free base)

Chemical Formula: C20H20BrN3O2S

Exact Mass: 445.0460

Molecular Weight: 446.36

Elemental Analysis: C, 53.82; H, 4.52; Br, 17.90; N, 9.41; O, 7.17; S, 7.18

Price and Availability

Size	Price	Availability
50mg	USD 250.00	2 Weeks
100mg	USD 450.00	2 Weeks
200mg	USD 750.00	2 Weeks
500mg	USD 1,650.00	2 Weeks
1g	USD 2,650.00	2 Weeks

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Related CAS #

127243-85-0 (free base) 130964-39-5 (2HCl) 1000995-75-4 (free base) 1049740-55-7 (2HCl hydrate)

Synonym

H-89 free base; H-89; H 89; H89; PKA Inhibitor; Protein kinase inhibitor H89

IUPAC/Chemical Name

N-[2-[[3-(4-Bromophenyl)-2-propen-1-yl]amino]ethyl]-5-Isoquinolinesulfonamide

InChi Key

ZKZXNDJNWUTGDK-NSCUHMNNSA-N

InChi Code

InChI=1S/C20H20BrN3O2S/c21-18-8-6-16(7-9-18)3-2-11-22-13-14-24-27(25,26)20-5-1-4-17-15-23-12-10-19(17)20/h1-10,12,15,22,24H,11,13-14H2/b3-2+

SMILES Code

O=S(C1=CC=CC2=C1C=CN=C2)(NCCNC/C=C/C3=CC=C(Br)C=C3)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

H-89 is a potent and selective inhibitor of cyclic AMP-dependent protein kinase (protein kinase A) with IC50 of 48 nM.

In vitro activity:

Mouse embryonic fibroblast (MEF), human bronchial epithelial (hBE), human bone osteosarcoma epithelial (U20S), hepatocellular carcinoma (HepG2), human pancreatic carcinoma (MIA PaCa-2), and mouse myoblast (C2C12) cells were also resistant to rapamycin and Torin1 treatment when pretreated with H89. Taken together, H89 enhances S6K1 and AKT phosphorylation. Moreover, H89 can prevent rapamycin and Torin1 from inhibiting S6K1 and AKT phosphorylation. Reference: Biochem J. 2020 May 29;477(10):1847-1863. https://pubmed.ncbi.nlm.nih.gov/32347294/

In vivo activity:

In the presence of DSS (D) and DCa (DSS + C. albicans), mice showed a significant increase in inflammatory parameters. Although the inflammatory parameters increased during the development of colitis and overgrowth of C. albicans, H89 treatment significantly reduced the clinical and histological scores for inflammation when compared to those in the D or DCa groups (Figure 5A,B). Reference: Microorganisms. 2020 Dec 19;8(12):2039. https://pubmed.ncbi.nlm.nih.gov/33352792/

Preparing Stock Solutions

The following data is based on the product molecular weight 446.36 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Muñoz KJ, Wang K, Sheehan LM, Tan M, Sütterlin C. The Small Molecule H89 Inhibits Chlamydia Inclusion Growth and Production of Infectious Progeny. Infect Immun. 2021 Jun 16;89(7):e0072920. doi: 10.1128/IAI.00729-20. Epub 2021 Jun 16. PMID: 33820812; PMCID: PMC8373235. 2. Melick CH, Jewell JL. Small molecule H89 renders the phosphorylation of S6K1 and AKT resistant to mTOR inhibitors. Biochem J. 2020 May 29;477(10):1847-1863. doi: 10.1042/BCJ20190958. PMID: 32347294; PMCID: PMC7261416. 3. Dumortier C, Charlet R, Bettaieb A, Jawhara S. H89 Treatment Reduces Intestinal Inflammation and Candida albicans Overgrowth in Mice. Microorganisms. 2020 Dec 19;8(12):2039. doi: 10.3390/microorganisms8122039. PMID: 33352792; PMCID: PMC7766101. 4. Lyu Y, Xu W, Zhang J, Li M, Xiang Q, Li Y, Tan T, Ou Q, Zhang J, Tian H, Xu JY, Jin C, Gao F, Wang J, Li W, Rong A, Lu L, Xu GT. Protein Kinase A Inhibitor H89 Attenuates Experimental Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2020 Feb 7;61(2):1. doi: 10.1167/iovs.61.2.1. PMID: 32031573; PMCID: PMC7325625.

In vitro protocol:

In vivo protocol:

1. Dumortier C, Charlet R, Bettaieb A, Jawhara S. H89 Treatment Reduces Intestinal Inflammation and Candida albicans Overgrowth in Mice. Microorganisms. 2020 Dec 19;8(12):2039. doi: 10.3390/microorganisms8122039. PMID: 33352792; PMCID: PMC7766101. 2. Lyu Y, Xu W, Zhang J, Li M, Xiang Q, Li Y, Tan T, Ou Q, Zhang J, Tian H, Xu JY, Jin C, Gao F, Wang J, Li W, Rong A, Lu L, Xu GT. Protein Kinase A Inhibitor H89 Attenuates Experimental Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2020 Feb 7;61(2):1. doi: 10.1167/iovs.61.2.1. PMID: 32031573; PMCID: PMC7325625.

1: Pereira GR, Lorenzo PL, Carneiro GF, Bilodeau-Goeseels S, Kastelic J, Liu IK. A specific adenylyl cyclase inhibitor (DDA) and a cyclic AMP-dependent protein kinase inhibitor (H-89) block the action of equine growth hormone on in vitro maturation of equine oocytes. Zygote. 2015 Dec;23(6):795-801. doi: 10.1017/S0967199414000434. PubMed PMID: 25257826. 2: He H, Genovese KJ, Swaggerty CL, Nisbet DJ, Kogut MH. Nitric oxide as a biomarker of intracellular Salmonella viability and identification of the bacteriostatic activity of protein kinase A inhibitor H-89. PLoS One. 2013;8(3):e58873. doi: 10.1371/journal.pone.0058873. PubMed PMID: 23554945; PubMed Central PMCID: PMC3598854. 3: Parks RJ, Howlett SE. H-89 decreases the gain of excitation-contraction coupling and attenuates calcium sparks in the absence of beta-adrenergic stimulation. Eur J Pharmacol. 2012 Sep 15;691(1-3):163-72. doi: 10.1016/j.ejphar.2012.07.012. PubMed PMID: 22796673. 4: Pflug A, Johnson KA, Engh RA. Anomalous dispersion analysis of inhibitor flexibility: a case study of the kinase inhibitor H-89. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Aug 1;68(Pt 8):873-7. doi: 10.1107/S1744309112028655. PubMed PMID: 22869112; PubMed Central PMCID: PMC3412763. 5: Hosseini-Zare MS, Salehi F, Seyedi SY, Azami K, Ghadiri T, Mobasseri M, Gholizadeh S, Beyer C, Sharifzadeh M. 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. doi: 10.1016/j.ejphar.2011.09.026. PubMed PMID: 21946102. 6: Suzuki R, Niimura S. Hatching and distribution of actin filaments in mouse blastocysts whose activities of protein kinase A were suppressed by H-89. J Reprod Dev. 2010 Feb;56(1):103-9. PubMed PMID: 19881218. 7: Herbst KJ, Allen MD, Zhang J. The cAMP-dependent protein kinase inhibitor H-89 attenuates the bioluminescence signal produced by Renilla Luciferase. PLoS One. 2009 May 21;4(5):e5642. doi: 10.1371/journal.pone.0005642. PubMed PMID: 19461967; PubMed Central PMCID: PMC2680982. 8: Sharif R, Aghsami M, Gharghabi M, Sanati M, Khorshidahmad T, Vakilzadeh G, Mehdizadeh H, Gholizadeh S, Taghizadeh G, Sharifzadeh M. Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function. Behav Brain Res. 2017 Jan 1;316:115-124. doi: 10.1016/j.bbr.2016.08.040. PubMed PMID: 27555536. 9: Azimi L, Kachooeian M, Khodagholi F, Yans A, Heysieattalab S, Vakilzadeh G, Vosoughi N, Sanati M, Taghizadeh G, Sharifzadeh M. Protective effects of salicylate on PKA inhibitor (H-89)-induced spatial memory deficit via lessening autophagy and apoptosis in rats. Pharmacol Biochem Behav. 2016 Oct 27. pii: S0091-3057(16)30185-X. doi: 10.1016/j.pbb.2016.10.008. [Epub ahead of print] PubMed PMID: 27984096. 10: Zhao S, Yang J, Li C, Xing S, Yu Y, Liu S, Pu F, Ma D. [Protein kinase A inhibitor H-89 blocks polyploidization of SP600125-induced CMK cells by regulating phosphorylation of ribosomal protein S6 kinase 1]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 Oct;32(10):1321-1326. Chinese. PubMed PMID: 27667455. 11: Park WS, Son YK, Kim N, Youm JB, Warda M, Ko JH, Ko EA, Kang SH, Kim E, Earm YE, Han J. Direct modulation of Ca(2+)-activated K(+) current by H-89 in rabbit coronary arterial smooth muscle cells. Vascul Pharmacol. 2007 Feb;46(2):105-13. PubMed PMID: 17052962. 12: Sharifzadeh M, Aghsami M, Gholizadeh S, Tabrizian K, Soodi M, Khalaj S, Ranjbar A, Hosseini-Sharifabad A, Roghani A, Karimfar MH. Protective effects of chronic lithium treatment against spatial memory retention deficits induced by the protein kinase AII inhibitor H-89 in rats. Pharmacology. 2007;80(2-3):158-65. PubMed PMID: 17534126. 13: Kato Y, Ozaki N, Yamada T, Miura Y, Oiso Y. H-89 potentiates adipogenesis in 3T3-L1 cells by activating insulin signaling independently of protein kinase A. Life Sci. 2007 Jan 9;80(5):476-83. PubMed PMID: 17056071. 14: Pearman C, Kent W, Bracken N, Hussain M. H-89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes. Br J Pharmacol. 2006 Aug;148(8):1091-8. PubMed PMID: 16799649; PubMed Central PMCID: PMC1752020. 15: Alamdary SZ, Digaleh H, Khodagholi F. Dual contradictory effect of H-89 on neuronal retraction, death and inflammation in differentiated PC12 cells subjected to oxidative stress. J Mol Neurosci. 2013 Nov;51(3):1030-7. doi: 10.1007/s12031-013-0092-7. PubMed PMID: 23949609. 16: Sun Park W, Kyoung Son Y, Kim N, Boum Youm J, Joo H, Warda M, Ko JH, Earm YE, Han J. The protein kinase A inhibitor, H-89, directly inhibits KATP and Kir channels in rabbit coronary arterial smooth muscle cells. Biochem Biophys Res Commun. 2006 Feb 24;340(4):1104-10. PubMed PMID: 16403438. 17: Son YK, Park WS, Kim SJ, Earm YE, Kim N, Youm JB, Warda M, Kim E, Han J. Direct inhibition of a PKA inhibitor, H-89 on KV channels in rabbit coronary arterial smooth muscle cells. Biochem Biophys Res Commun. 2006 Mar 24;341(4):931-7. PubMed PMID: 16455049. 18: Makaula S, Lochner A, Genade S, Sack MN, Awan MM, Opie LH. H-89, a non-specific inhibitor of protein kinase A, promotes post-ischemic cardiac contractile recovery and reduces infarct size. J Cardiovasc Pharmacol. 2005 Apr;45(4):341-7. PubMed PMID: 15772523. 19: Meja KK, Catley MC, Cambridge LM, Barnes PJ, Lum H, Newton R, Giembycz MA. Adenovirus-mediated delivery and expression of a cAMP-dependent protein kinase inhibitor gene to BEAS-2B epithelial cells abolishes the anti-inflammatory effects of rolipram, salbutamol, and prostaglandin E2: a comparison with H-89. J Pharmacol Exp Ther. 2004 May;309(2):833-44. PubMed PMID: 14747610. 20: Chang CZ, Wu SC, Kwan AL, Lin CL. Magnesium Lithospermate B Implicates 3'-5'-Cyclic Adenosine Monophosphate/Protein Kinase A Pathway and N-Methyl-d-Aspartate Receptors in an Experimental Traumatic Brain Injury. World Neurosurg. 2015 Oct;84(4):954-63. doi: 10.1016/j.wneu.2015.05.075. PubMed PMID: 26093361.