Soluble guanylyl cyclase (sGC) activator. It activates guanylyl cyclase, inducing the transformation of GTP to cGMP. [3]

Ataciguat (1-100 μM) causes the coronary or aortic artery rings to relax [2]. In HUVEC cells, ataciguat (0.1–10 μM; 30 minutes) boosts NO production [2]. High-concentration biliary contractions are induced in the carbachine-precontracted circular sphincter of Oddi (SO) by ataciguat (1 nM-100 μM). [3].

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Ataciguat (10⁻⁹ - 10⁻⁴ mol/L) induces significant, concentration-dependent relaxation in isolated sheep sphincter of Oddi (SO) rings that have been pre-contracted with carbachol (10⁻⁶ mol/L) (p = 0.0018). [3]
The relaxant effect of ataciguat is significantly greater than that of zaprinast at all concentrations tested (p = 0.0024). The mean maximal inhibition (Emax) value for ataciguat-induced relaxation is 79.2 ± 5.8% of the carbachol-induced contraction. Its pD₂ value (-log EC50) is 6.52 ± 0.10. [3]
The relaxation response induced by ataciguat is significantly decreased in the presence of the soluble guanylyl cyclase inhibitor ODQ (10⁻⁵ mol/L), starting from the 10⁻⁸ mol/L concentration (p = 0.0012). In the presence of ODQ, the Emax of ataciguat is reduced to 20.6 ± 3.0%. [3]

HUVECs were cultured in DMEM supplemented with 10% fetal calf serum and antibiotics at 37°C in a 5% CO₂ atmosphere. For NO measurement by fluorescence, cells were plated in 96-well plates at a density of 5 × 10⁴ cells per well and incubated for 24 hours. After treatment, cells were washed with PBS and incubated with the selective fluorescent probe DAF-2T (10 μM) for 30 minutes. The reaction of DAF-2T with N₂O₃ (an oxidation product of NO) produces the fluorescent compound DAF-2T. Fluorescence intensity was measured using a fluorometer at excitation and emission wavelengths of 435 nm and 538 nm, respectively. HUVECs were treated with PBS (control), ataciguat (0.1, 1, and 10 μM) for 30 minutes. To investigate the mechanism, cells were also treated with ataciguat (0.1 μM) in the presence of the NOS inhibitor L-NAME (1 μM) or the calcium channel blocker verapamil. [2]
For NO quantification by electrode, HUVECs were plated in 6-well plates at a density of 4 × 10⁵ cells per well. After 24 hours, cells were treated for 30 minutes. The supernatant was then collected and added to a vessel containing a working solution (deionized water, 1M sulfuric acid, and 90 mM potassium iodide) which reduces nitrite (NO₂⁻, a stable NO metabolite) to NO. The NO produced was measured using a selective NO electrode (InNO-T-II). A calibration curve for nitrite was performed before each experiment. This method was used to confirm the effect of the cGMP analogue 8-Br-cGMP, not directly for ataciguat. [2]

The study is an ex vivo pharmacological investigation. Tissue samples were obtained from ten adult male Anatolian Akkaraman sheep, weighing 38-45 kg. The sheep were sacrificed, and the sphincter of Oddi was quickly removed. The SO was placed in a pre-aerated (95% O2 and 5% CO2) Krebs' bicarbonate solution for transport to the laboratory. [3]
Tissue Bath Protocol:** The SO was dissected into rings and mounted in 10 mL tissue baths containing the aerated Krebs' solution maintained at 37°C. Each ring was tied to an isometric transducer (Grass FT 03) under a resting tension of 1.5 g. The tissues were allowed to equilibrate for 60-90 minutes, during which the bath solution was changed every 15 minutes. After equilibration, the rings were contracted with a submaximal concentration of carbachol (10⁻⁶ mol/L). Once a stable contraction was achieved, cumulative concentration-response curves to ataciguat (10⁻⁹ to 10⁻⁴ mol/L) were obtained. To investigate the mechanism, the effect of ataciguat was also tested in the presence of the sGC inhibitor ODQ (10⁻⁵ mol/L), which was added to the bath prior to ataciguat administration. Between each drug application, the tissues were washed at least twice and allowed to re-equilibrate for at least 30 minutes. [3]

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The study is an ex vivo pharmacological investigation. Tissue samples were obtained from ten adult male Anatolian Akkaraman sheep, weighing 38-45 kg. The sheep were sacrificed, and the sphincter of Oddi was quickly removed. The SO was placed in a pre-aerated (95% O2 and 5% CO2) Krebs' bicarbonate solution for transport to the laboratory. [3]
Tissue Bath Protocol: The SO was dissected into rings and mounted in 10 mL tissue baths containing the aerated Krebs' solution maintained at 37°C. Each ring was tied to an isometric transducer (Grass FT 03) under a resting tension of 1.5 g. The tissues were allowed to equilibrate for 60-90 minutes, during which the bath solution was changed every 15 minutes. After equilibration, the rings were contracted with a submaximal concentration of carbachol (10⁻⁶ mol/L). Once a stable contraction was achieved, cumulative concentration-response curves to ataciguat (10⁻⁹ to 10⁻⁴ mol/L) were obtained. To investigate the mechanism, the effect of ataciguat was also tested in the presence of the sGC inhibitor ODQ (10⁻⁵ mol/L), which was added to the bath prior to ataciguat administration. Between each drug application, the tissues were washed at least twice and allowed to re-equilibrate for at least 30 minutes. [3]

[1]. Biochemistry and pharmacology of novel anthranilic acid derivatives activating heme-oxidized soluble guanylyl cyclase. Mol Pharmacol. 2006 Apr;69(4):1260-8.

[2]. In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation. J Pharm Pharm Sci. 2018;21(1):38-45.

[3]. Comparative Relaxant Effects of Ataciguat and Zaprinast on Sheep Sphincter of Oddi. Balkan Med J. 2016 Jul;33(4):453-7.

Ataciguat has been used in basic scientific research on aortic stenosis.

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Ataciguat is described as an aminobenzoic acid derivative and a novel soluble guanylyl cyclase (sGC) activator. Its mechanism of action involves activating guanylyl cyclase, which leads to the conversion of GTP to cGMP. The subsequent increase in cGMP activates protein kinase G, which reduces intracellular ionized calcium concentration and calcium sensitivity in smooth muscle cells, ultimately causing smooth muscle relaxation. [3]
This study is the first to investigate the effect of ataciguat on the gastrointestinal system and specifically on the sphincter of Oddi. The results suggest that ataciguat, by potently relaxing the SO, could be a candidate agent for local application during Endoscopic Retrograde Cholangiopancreatography (ERCP) procedures to facilitate cannulation and potentially reduce post-ERCP complications like pancreatitis. [3]

574.981

254877-67-3

254877-67-3;254976-06-2 (Sodium);

213037

White to off-white solid powder

1.6±0.1 g/cm3

1.685

6.08

2

9

7

35

944

0

O=C(NC1=CC=C(S(=O)(N2CCOCC2)=O)C=C1)C3=CC(Cl)=CC=C3NS(=O)(C4=CC=C(Cl)S4)=O

PQHLRGARXNPFCF-UHFFFAOYSA-N

InChI=1S/C21H19Cl2N3O6S3/c22-14-1-6-18(25-34(28,29)20-8-7-19(23)33-20)17(13-14)21(27)24-15-2-4-16(5-3-15)35(30,31)26-9-11-32-12-10-26/h1-8,13,25H,9-12H2,(H,24,27)

5-chloro-2-[(5-chlorothiophen-2-yl)sulfonylamino]-N-(4-morpholin-4-ylsulfonylphenyl)benzamide

HMR-1766 HMR1766 HMR 1766

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~173.46 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)