17-ODYA is a selective inhibitor of cytochrome P450 ω-hydroxylases (CYPω-hydroxylases), enzymes that catalyze the ω-hydroxylation of arachidonic acid to form 20-hydroxyeicosatetraenoic acid (20-HETE) [3].
It acts as a suicide-substrate inhibitor of CYP fatty acid ω-hydroxylases [3].

In heart tissue microsome studies, incubation with 17-ODYA (10⁻⁵ mol/L) for 5 minutes before addition of [¹⁴C]arachidonic acid significantly inhibited the production of 20-HETE. The radioactive peak corresponding to 20-HETE was decreased by 81.7% (to 18.3 ± 4.9% of control) in microsomes treated with 17-ODYA [3].

Renal 17-ODYA (0.28 mg/kg; intracoronary; infusion over 2 to 3 minutes; dog) significantly inhibits 20-HETE production during local reperfusion and produces a significant reduction in myocardial infarction. This is associated with increased renal papillary blood flow, renal blood flow, and renal small blood flow when infusion of 17-ODYA (16.5 nmol/min) directly into the renal interstitium of the kidney causes diuresis and natriuresis [3].

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In a canine model of myocardial ischemia-reperfusion injury, 17-ODYA was administered by intracoronary infusion 15 minutes before a 60-minute left anterior descending coronary artery occlusion followed by 3 hours of reperfusion [3].
At a dose of 0.28 mg/kg, 17-ODYA markedly inhibited 20-HETE production during ischemia and reperfusion, with plasma 20-HETE concentrations significantly reduced compared to control at all time points measured [3].
17-ODYA at 0.28 mg/kg significantly reduced myocardial infarct size to 5.9 ± 2.2% of the area at risk, compared to 19.6 ± 1.7% in the control group (P < 0.05). At a lower dose of 0.07 mg/kg, 17-ODYA showed a trend toward reduced 20-HETE concentration and infarct size, but these changes were not statistically significant [3].
Hemodynamic parameters (heart rate, mean arterial blood pressure, pressure-rate product) and regional myocardial blood flow were not significantly different between 17-ODYA-treated groups and control group, indicating that the cardioprotective effect was not due to hemodynamic changes or differences in collateral blood flow [3].

Heart tissue microsomes were prepared by homogenization in buffer containing 0.1 mol/L phosphate buffer (pH 7.7), 250 mmol/L sucrose, 1 mmol/L EDTA, and complete protease inhibitor, followed by centrifugation at 9,000g for 10 minutes and then at 10,000g for 1.5 hours. The pellet was resuspended in 0.5 mol/L phosphate buffer (pH 7.25) containing 1 mmol/L EDTA, 0.01 mmol/L dithiothreitol, 30% glycerol, and complete protease inhibitor. The reaction was incubated in 400 μL assay buffer (0.1 mol/L phosphate buffer, pH 7.4, 1 mmol/L EDTA, 10 mmol/L MgCl₂) containing 100 μg protein, 1 mmol/L NADPH, 10 mmol/L isocitrate, and 0.1 U/mL isocitrate dehydrogenase. The solution was incubated with or without 10⁻⁵ mol/L 17-ODYA for 5 minutes before addition of [¹⁴C]arachidonic acid for 30 minutes. Samples were extracted by solid phase extraction and separated on a C₁₈ reverse phase column using water:acetonitrile containing 0.1% acetic acid as mobile phase at a flow rate of 1.0 mL/min. The mobile phase gradient started with 50% acetonitrile and linearly increased to 100% acetonitrile over 35 minutes. Fractions were collected and radioactivity was counted on a scintillation counter. The retention time of the radioactive peak of 20-HETE in the sample was compared with the 20-HETE standard [3].

Adult mongrel dogs of either sex weighing 15-25 kg were used. Dogs were anesthetized with pentobarbital (30 mg/kg intravenously), intubated, and ventilated with room air supplemented with oxygen. A left thoracotomy was performed at the fifth intercostal space, and the heart was suspended in a pericardial cradle. The left anterior descending coronary artery was isolated distal to the first diagonal branch for later occlusion. Catheters were placed in the aorta for blood pressure measurement and blood sampling, in the left atrium for microsphere injection, and in the great cardiac vein for venous blood sampling. Dogs were randomly assigned to treatment groups. Fifteen minutes before the 60-minute LAD occlusion period, 17-ODYA (0.07 or 0.28 mg/kg) or vehicle was administered by intracoronary infusion over 2-3 minutes. Hemodynamic measurements, blood gas analyses, and myocardial blood flow measurements were performed at baseline and at 30 minutes into the occlusion period. After 60 minutes of occlusion, the LAD was reperfused for 3 hours. At the end of reperfusion, hearts were electrically fibrillated, removed, and prepared for infarct size determination and regional myocardial blood flow measurement [3].
For infarct size determination, the LAD was cannulated. Five mL of Patent blue dye and 5 mL saline were injected at equal pressure into the left atrium and LAD, respectively, to determine the area at risk and nonischemic area. The left ventricle was sliced into serial transverse sections 6-7 mm thick. The nonstained ischemic area and blue-stained normal area were separated and incubated with 1% triphenyltetrazolium chloride in 0.1 mol/L phosphate buffer (pH 7.4) at 37°C for 15 minutes. After overnight incubation in 10% formaldehyde, noninfarcted and infarcted tissues within the area at risk were separated and weighed. Infarct size was expressed as a percentage of the area at risk [3].

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Adult mongrel dogs of either sex weighing 15-25 kg were used. Dogs were anesthetized with pentobarbital (30 mg/kg intravenously), intubated, and ventilated with room air supplemented with oxygen. A left thoracotomy was performed at the fifth intercostal space, and the heart was suspended in a pericardial cradle. The left anterior descending coronary artery was isolated distal to the first diagonal branch for later occlusion. Catheters were placed in the aorta for blood pressure measurement and blood sampling, in the left atrium for microsphere injection, and in the great cardiac vein for venous blood sampling. Dogs were randomly assigned to treatment groups. Fifteen minutes before the 60-minute LAD occlusion period, 17-ODYA (0.07 or 0.28 mg/kg) or vehicle was administered by intracoronary infusion over 2-3 minutes. Hemodynamic measurements, blood gas analyses, and myocardial blood flow measurements were performed at baseline and at 30 minutes into the occlusion period. After 60 minutes of occlusion, the LAD was reperfused for 3 hours. At the end of reperfusion, hearts were electrically fibrillated, removed, and prepared for infarct size determination and regional myocardial blood flow measurement [3].
For infarct size determination, the LAD was cannulated. Five mL of Patent blue dye and 5 mL saline were injected at equal pressure into the left atrium and LAD, respectively, to determine the area at risk and nonischemic area. The left ventricle was sliced into serial transverse sections 6-7 mm thick. The nonstained ischemic area and blue-stained normal area were separated and incubated with 1% triphenyltetrazolium chloride in 0.1 mol/L phosphate buffer (pH 7.4) at 37°C for 15 minutes. After overnight incubation in 10% formaldehyde, noninfarcted and infarcted tissues within the area at risk were separated and weighed. Infarct size was expressed as a percentage of the area at risk [3].

[1]. β-adrenergic Receptor-stimulated Cardiac Myocyte Apoptosis: Role of Cytochrome P450 ω-hydroxylase. J Cardiovasc Pharmacol. 2017;70(2):94-101.

[2]. Effects of 17-octadecynoic acid, a suicide-substrate inhibitor of cytochrome P450 fatty acid omega-hydroxylase, on renal function in rats. J Pharmacol Exp Ther. 1994;268(1):474-481.

[3]. Inhibition of cytochrome P450omega-hydroxylase: a novel endogenous cardioprotective pathway. Circ Res. 2004;95(8):e65-e71.

Octadec-17-ynoic acid is an alkyne fatty acid formed by the didehydrogenation reaction of octadecanoic acid (stearic acid) at positions 17 and 18. It functions as a P450 inhibitor, an EC 1.14.14.94 (leukotriene B4 20-monooxygenase) inhibitor, and an EC 1.14.15.3 (alkane 1-monooxygenase) inhibitor. It is a long-chain fatty acid, an alkyne fatty acid, a terminal alkyne compound, and a monounsaturated fatty acid.

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17-ODYA (17-octadecynoic acid) is a widely recognized specific inhibitor of cytochrome P450 ω-hydroxylases. It has been shown to inhibit CYP ω-hydroxylases in various tissues including kidney and heart [3].
In this study, 17-ODYA was used as a pharmacological tool to investigate the role of CYPω-hydroxylases and their metabolite 20-HETE in myocardial ischemia-reperfusion injury. The results demonstrate that inhibition of 20-HETE production by 17-ODYA produces a profound cardioprotective effect, reducing infarct size by approximately 70% compared to control [3].
Western blot analysis confirmed the presence of several CYPω-hydroxylase isoforms in canine heart tissue that can produce 20-HETE, including CYP4A1, CYP4A2, and CYP4F. The membrane fractions showed immunoreactive bands for these enzymes at 48-50 kDa, with greater intensity than cytosolic fractions [3].
The study provides the first evidence that CYPω-hydroxylases and their major arachidonic acid metabolite, 20-HETE, play an important endogenous role in exacerbating myocardial injury during ischemia-reperfusion. Inhibition of this pathway with selective inhibitors like 17-ODYA represents a potential new therapeutic strategy for reducing ischemia-reperfusion injury in patients with ischemic heart disease [3].

C18H32O2

280.44548

280.24

34450-18-5

1449

White to off-white solid powder

0.9±0.1 g/cm3

400.8±18.0 °C at 760 mmHg

142-148 °C(lit.)

194.7±15.9 °C

0.0±2.0 mmHg at 25°C

1.470

6.86

1

2

15

20

262

0

DZIILFGADWDKMF-UHFFFAOYSA-N

InChI=1S/C18H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h1H,3-17H2,(H,19,20)

octadec-17-ynoic acid

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 : ~25 mg/mL (~89.14 mM)

Solubility in Formulation 1: 2.5 mg/mL (8.91 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (8.91 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.)