HA-1004 HCl
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MedKoo CAT#: 526339

CAS#: 92564-08-4 (2HCl),

Description: HA-1004 is an inhibitor of PKA, cGKI, PKC, MYLK, and calcium channel protein.


Chemical Structure

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HA-1004 HCl
CAS# 92564-08-4 (2HCl),

Theoretical Analysis

MedKoo Cat#: 526339
Name: HA-1004 HCl
CAS#: 92564-08-4 (2HCl),
Chemical Formula: C12H17Cl2N5O2S
Exact Mass: 365.048
Molecular Weight: 366.261
Elemental Analysis: C, 39.35; H, 4.68; Cl, 19.36; N, 19.12; O, 8.74; S, 8.75

Price and Availability

Size Price Availability Quantity
5.0mg USD 250.0 2 Weeks
10.0mg USD 450.0 2 Weeks
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Related CAS #: 91742-10-8 (free base)   92564-34-6 (HCl)   92564-08-4 (2HCl)    

Synonym: HA-1004; HA 1004; HA1004; HA-1004 HCl; HA-1004 dihydrochloride;

IUPAC/Chemical Name: N-(2-Guanidinoethyl)-5-isoquinolinesulfonamide Dihydrochloride

InChi Key: PMTUBVLLVFJRLK-UHFFFAOYSA-N

InChi Code: InChI=1S/C12H15N5O2S.2ClH/c13-12(14)16-6-7-17-20(18,19)11-3-1-2-9-8-15-5-4-10(9)11;;/h1-5,8,17H,6-7H2,(H4,13,14,16);2*1H

SMILES Code: O=S(C1=CC=CC2=C1C=CN=C2)(NCCNC(N)=N)=O.[H]Cl.[H]Cl

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

Product Data:

Certificate of Analysis:

Safety Data Sheet (SDS):

Biological target: An inhibitor of PKG and PKA.
In vitro activity: In vitro, HA 1004, verapamil, nifedipine and albuterol inhibited Ca2+-induced contractions of the depolarized guinea pig trachea. HA 1004 and albuterol also relaxed the basal tracheal tone, whereas verapamil and nifedipine were inactive. Reference: Pharmacology. 1988;37(3):187-94. https://pubmed.ncbi.nlm.nih.gov/2906438/
In vivo activity: As shown in Figure 2A, chronic pre-treatment with HA-1004 concomitantly with morphine antagonized the expression of PKA in both controls and morphine-withdrawn animals. Reference: Front Pharmacol. 2013 Dec 27;4:164. https://pubmed.ncbi.nlm.nih.gov/24409147/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 2.0 5.46
DMSO 3.0 8.19
PBS (pH 7.2) 5.0 13.65

Preparing Stock Solutions

The following data is based on the product molecular weight 366.261 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.

Recalculate based on batch purity %
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. Chapman RW, Tozzi S, Kreutner W. Antibronchoconstrictor activity of the intracellular calcium antagonist HA 1004 in guinea pigs. Pharmacology. 1988;37(3):187-94. doi: 10.1159/000138462. PMID: 2906438. 2. Ishikawa T, Inagaki M, Watanabe M, Hidaka H. Relaxation of vascular smooth muscle by HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinase. J Pharmacol Exp Ther. 1985 Nov;235(2):495-9. PMID: 2997436. 3. Almela P, García-Carmona JA, Martínez-Laorden E, Milanés MV, Laorden ML. Crosstalk between G protein-coupled receptors (GPCRs) and tyrosine kinase receptor (TXR) in the heart after morphine withdrawal. Front Pharmacol. 2013 Dec 27;4:164. doi: 10.3389/fphar.2013.00164. PMID: 24409147; PMCID: PMC3873507. 4. Almela P, Atucha NM, Milanés MV, Laorden ML. Cross-talk between protein kinase A and mitogen-activated protein kinases signalling in the adaptive changes observed during morphine withdrawal in the heart. J Pharmacol Exp Ther. 2009 Sep;330(3):771-82. doi: 10.1124/jpet.109.154583. Epub 2009 Jun 30. PMID: 19567779.
In vitro protocol: 1. Chapman RW, Tozzi S, Kreutner W. Antibronchoconstrictor activity of the intracellular calcium antagonist HA 1004 in guinea pigs. Pharmacology. 1988;37(3):187-94. doi: 10.1159/000138462. PMID: 2906438. 2. Ishikawa T, Inagaki M, Watanabe M, Hidaka H. Relaxation of vascular smooth muscle by HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinase. J Pharmacol Exp Ther. 1985 Nov;235(2):495-9. PMID: 2997436.
In vivo protocol: 1. Almela P, García-Carmona JA, Martínez-Laorden E, Milanés MV, Laorden ML. Crosstalk between G protein-coupled receptors (GPCRs) and tyrosine kinase receptor (TXR) in the heart after morphine withdrawal. Front Pharmacol. 2013 Dec 27;4:164. doi: 10.3389/fphar.2013.00164. PMID: 24409147; PMCID: PMC3873507. 2. Almela P, Atucha NM, Milanés MV, Laorden ML. Cross-talk between protein kinase A and mitogen-activated protein kinases signalling in the adaptive changes observed during morphine withdrawal in the heart. J Pharmacol Exp Ther. 2009 Sep;330(3):771-82. doi: 10.1124/jpet.109.154583. Epub 2009 Jun 30. PMID: 19567779.

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1: Almela P, García-Carmona JA, Martínez-Laorden E, Milanés MV, Laorden ML. Crosstalk between G protein-coupled receptors (GPCRs) and tyrosine kinase receptor (TXR) in the heart after morphine withdrawal. Front Pharmacol. 2013 Dec 27;4:164. doi: 10.3389/fphar.2013.00164. eCollection 2013. PubMed PMID: 24409147; PubMed Central PMCID: PMC3873507.

2: Villarruel EQ, Borda E, Sterin-Borda L, Orman B. Lidocaine-induced apoptosis of gingival fibroblasts: participation of cAMP and PKC activity. Cell Biol Int. 2011 Aug;35(8):783-8. doi: 10.1042/CBI20100200. PubMed PMID: 21047305.

3: Almela P, Atucha NM, Milanés MV, Laorden ML. Cross-talk between protein kinase A and mitogen-activated protein kinases signalling in the adaptive changes observed during morphine withdrawal in the heart. J Pharmacol Exp Ther. 2009 Sep;330(3):771-82. doi: 10.1124/jpet.109.154583. Epub 2009 Jun 30. PubMed PMID: 19567779.

4: Varga F, Rumpler M, Spitzer S, Karlic H, Klaushofer K. Osteocalcin attenuates T3- and increases vitamin D3-induced expression of MMP-13 in mouse osteoblasts. Endocr J. 2009;56(3):441-50. Epub 2009 Feb 18. PubMed PMID: 19225217.

5: Almela P, Victoria Milanés M, Luisa Laorden M. Tyrosine hydroxylase phosphorylation after naloxone-induced morphine withdrawal in the left ventricle. Basic Res Cardiol. 2009 Jul;104(4):366-76. doi: 10.1007/s00395-008-0768-2. Epub 2008 Dec 22. PubMed PMID: 19104749.

6: Almela P, Milanés M, Laorden M. The PKs PKA and ERK 1/2 are involved in phosphorylation of TH at Serine 40 and 31 during morphine withdrawal in rat hearts. Br J Pharmacol. 2008 Sep;155(1):73-83. doi: 10.1038/bjp.2008.224. Epub 2008 Jun 9. PubMed PMID: 18536752; PubMed Central PMCID: PMC2527841.

7: Almela P, Cerezo M, González-Cuello A, Milanés MV, Laorden ML. Differential involvement of 3', 5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos and tyrosine hydroxylase expression in the heart after naloxone induced morphine withdrawal. Naunyn Schmiedebergs Arch Pharmacol. 2007 Jan;374(4):293-303. Epub 2006 Nov 25. PubMed PMID: 17216288.

8: Schach C, Xu M, Platoshyn O, Keller SH, Yuan JX. Thiol oxidation causes pulmonary vasodilation by activating K+ channels and inhibiting store-operated Ca2+ channels. Am J Physiol Lung Cell Mol Physiol. 2007 Mar;292(3):L685-98. Epub 2006 Nov 10. PubMed PMID: 17098807.

9: Ghosh M, Gharami K, Paul S, Das S. Thyroid hormone-induced morphological differentiation and maturation of astrocytes involves activation of protein kinase A and ERK signalling pathway. Eur J Neurosci. 2005 Oct;22(7):1609-17. PubMed PMID: 16197501.

10: Broccardo CJ, Billings RE, Andersen ME, Hanneman WH. Probing the control elements of the CYP1A1 switching module in H4IIE hepatoma cells. Toxicol Sci. 2005 Nov;88(1):82-94. Epub 2005 Aug 4. PubMed PMID: 16081525.

11: Kochel I, Rapak A, Ziolo E, Strzadala L. Nur77 nuclear import and its NBRE-binding activity in thymic lymphoma cells are regulated by different mechanisms sensitive to FK506 or HA1004. Biochem Biophys Res Commun. 2005 Sep 9;334(4):1102-6. PubMed PMID: 16051191.

12: Kubo T, Hagiwara Y. Protein kinase C activation-induced increases of neural activity are enhanced in the hypothalamus of spontaneously hypertensive rats. Brain Res. 2005 Feb 8;1033(2):157-63. PubMed PMID: 15694920.

13: Benavides M, Laorden ML, Milanés MV. Involvement of 3',5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos expression and tyrosine hydroxylase levels during morphine withdrawal in the hypothalamic paraventricular nucleus and medulla oblongata catecholaminergic cell groups. J Neurochem. 2005 Jan;92(2):246-54. PubMed PMID: 15663473.

14: Shen KZ, Johnson SW. Group II metabotropic glutamate receptor modulation of excitatory transmission in rat subthalamic nucleus. J Physiol. 2003 Dec 1;553(Pt 2):489-96. Epub 2003 Sep 18. PubMed PMID: 14500768; PubMed Central PMCID: PMC2343573.

15: Wainszelbaum MJ, Belaunzarán ML, Lammel EM, Florin-Christensen M, Florin-Christensen J, Isola EL. Free fatty acids induce cell differentiation to infective forms in Trypanosoma cruzi. Biochem J. 2003 Nov 1;375(Pt 3):705-12. PubMed PMID: 12887332; PubMed Central PMCID: PMC1223715.

16: Miyoshi K, Kawakami N, Horio S, Fukui H. Inhibition of histamine H1 receptor downregulation by KT5823, a protein kinase G inhibitor. Methods Find Exp Clin Pharmacol. 2003 Jun;25(5):343-7. PubMed PMID: 12851655.

17: Kalas W, Matuszyk J, Ziolo E, Strzadala L. FK506 restores sensitivity of thymic lymphomas to calcium-mediated apoptosis and the inducible expression of Fas ligand. Anticancer Res. 2003 Mar-Apr;23(2B):1613-7. PubMed PMID: 12820430.

18: Martínez MD, Milanés MV, Laorden ML. Implication of the signal transduction pathways in the enhancement of noradrenaline turnover induced by morphine withdrawal in the heart. Eur J Pharmacol. 2003 Jun 20;471(2):113-9. PubMed PMID: 12818698.

19: Cerezo M, Laorden ML, Milanés MV. Inhibition of protein kinase C but not protein kinase A attenuates morphine withdrawal excitation of rat hypothalamus-pituitary-adrenal axis. Eur J Pharmacol. 2002 Sep 27;452(1):57-66. PubMed PMID: 12323385.

20: Matuszyk J, Cebrat M, Kalas W, Strzadala L. HA1004, an inhibitor of serine/threonine protein kinases, restores the sensitivity of thymic lymphomas to Ca2+-mediated apoptosis through a protein kinase A-independent mechanism. Int Immunopharmacol. 2002 Mar;2(4):435-42. PubMed PMID: 11962723.