| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
ATP-sensitive potassium (KATP) channels, specifically the sulfonylurea receptor 2 (SUR2)-associated KATP channels (SUR2-KIR6). P-1075 is a potent and selective activator of KATP channels with an EC50 of 45 nM. KATP channels are octameric complexes composed of four inwardly rectifying potassium channel subunits (Kir6.x) and four sulfonylurea receptor subunits (SURx). These channels couple cellular metabolism to membrane excitability by sensing changes in intracellular ATP and ADP levels. P-1075 specifically targets SUR2-containing KATP channels, which are predominantly expressed in cardiac and smooth muscle tissues. By binding to the SUR2 subunit, P-1075 promotes channel opening, leading to potassium efflux, membrane hyperpolarization, and reduced cellular excitability. This mechanism of action underlies the compound's cardioprotective and vasodilatory effects. P-1075 is widely used to dissect KATP-mediated signal transduction, preconditioning mechanisms, and myocardial protection pathways. The compound is also used to evaluate KATP-targeted therapeutic strategies under ischemia-reperfusion and oxidative stress conditions. P-1075 produces reactive oxygen species (ROS) by opening mitochondrial KATP channels, which contributes to its cardioprotective effects.
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| ln Vitro |
Through competitive binding assays, P1075 (3 nM) causes a monophasic inhibition curve in the presence of MgATP [1]. In rabbit cardiomyocytes, P1075 (100 µM; 10 min) produces ROS in a KATP-dependent way [2]. In isolated rabbit hearts, P1075 (150 nM) decreased the extent of infarcts when compared to control animals (area at risk: 10.6% vs. 31.5%, P < 0.05) [2].
P-1075 demonstrates potent activation of KATP channels in various in vitro preparations. The compound activates SUR2-containing KATP channels with an EC50 of 45 nM. In electrophysiological studies using patch-clamp techniques, P-1075 increases KATP channel open probability in a concentration-dependent manner. The compound's effects are more pronounced on SUR2A-containing channels (cardiac type) compared to SUR2B-containing channels (smooth muscle type). P-1075 has been shown to produce reactive oxygen species (ROS) by opening mitochondrial KATP channels in rabbit hearts, which contributes to its cardioprotective effects. The compound also induces vasodilation in isolated blood vessel preparations by activating smooth muscle KATP channels. In addition, P-1075 has been used to study the role of KATP channels in neuronal excitability and neurotransmitter release. The compound's potent and selective activation of SUR2-containing KATP channels makes it a valuable tool for studying the physiological and pathophysiological roles of KATP channels in various tissues. |
| ln Vivo |
In ischemia models, P1075 (iv; 1 μg/kg; once) therapy resulted in a smaller infarct [3].
P-1075 is widely used in cardiovascular research to study KATP channel-mediated effects in vivo. The compound has been shown to produce cardioprotective effects in animal models of ischemia-reperfusion injury. By opening mitochondrial KATP channels, P-1075 produces reactive oxygen species that trigger preconditioning-like protective mechanisms, reducing infarct size and improving cardiac function. The compound also induces vasodilation in vivo, leading to reduced blood pressure and increased blood flow. P-1075 has been used to evaluate KATP-targeted therapeutic strategies under ischemia-reperfusion and oxidative stress conditions. The compound's effects on KATP channels in various tissues have been characterized in numerous preclinical studies. However, P-1075 has not been approved for clinical use, and its in vivo pharmacokinetics and safety profile require further characterization. The compound is intended for research use only and is not for human therapeutic use. |
| Enzyme Assay |
KATP channel activity assays are performed using electrophysiological techniques, including patch-clamp and voltage-clamp recordings. Cells expressing recombinant KATP channels (e.g., HEK-293 cells co-expressing Kir6.2 and SUR2A or SUR2B) are used to assess channel activity. P-1075 is applied at various concentrations (0.1 nM to 10 μM), and channel currents are recorded in response to voltage steps or ramps. The EC50 for P-1075-induced channel activation is 45 nM. Alternatively, rubidium (Rb+) efflux assays or thallium (Tl+) flux assays can be used to measure KATP channel activity in a high-throughput format. In these assays, cells are loaded with Rb+ or Tl+ and the efflux or influx is measured in the presence of P-1075. Mitochondrial KATP channel activity can be assessed by measuring mitochondrial membrane potential using fluorescent dyes (e.g., JC-1 or TMRM) or by measuring ROS production using fluorescent probes (e.g., DCFH-DA). Appropriate positive controls (e.g., diazoxide or pinacidil) and vehicle controls are included to validate the assay systems.
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| Cell Assay |
Cell viability assay [1]
Cell Types: COS-7 Cell Tested Concentrations: 3-15 nM Incubation Duration: Experimental Results: The IC50 value is 15 nM and the Hill coefficient is 1.0. Cell viability assay [2] Cell Types: Adult rabbit cardiomyocytes Tested Concentrations: 100 µM Incubation Duration: 10 minutes Experimental Results: Resulted in a 44% increase in ROS production (P<0.001 compared to untreated cells). Cellular KATP channel activation is evaluated in various cell types, including cardiac myocytes, smooth muscle cells, and neuronal cells. Cells are cultured in appropriate media at 37°C with 5% CO₂ and treated with P-1075 at concentrations ranging from 0.1 nM to 10 μM for 15-60 minutes. Membrane potential is measured using fluorescent voltage-sensitive dyes (e.g., DiBAC₄(3) or FLIPR Membrane Potential Dye). Alternatively, intracellular potassium levels can be measured using ion-selective electrodes or fluorescent potassium indicators (e.g., PBFI). ROS production is measured using DCFH-DA or other fluorescent probes. Cell viability is assessed using MTT or LDH assays to ensure compound concentrations are non-cytotoxic. In cardiac myocytes, P-1075-induced KATP channel activation is assessed by measuring action potential duration or contractile function. Each experiment includes vehicle controls (DMSO) and appropriate positive controls (e.g., diazoxide, pinacidil). |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats, ischemia for 30 minutes, reperfusion for 2 hrs (hrs (hours)) [3]
Doses: 1μg/kg Route of Administration: intravenous (iv) (iv)injection; reperfusion after 2 hrs (hrs (hours)). 1 microgram/kg; Experimental Results: Infarct size was diminished (41.8%) compared to vehicle. In vivo efficacy of P-1075 is evaluated in animal models of ischemia-reperfusion injury, myocardial infarction, and other cardiovascular conditions. The compound is administered intravenously or intraperitoneally at doses determined by preclinical studies. In ischemia-reperfusion models, animals (e.g., rats or rabbits) are subjected to coronary artery occlusion followed by reperfusion. P-1075 is administered before or during ischemia, and infarct size is measured by TTC staining. Cardiac function is assessed by echocardiography or hemodynamic measurements. ROS production in the heart is measured using fluorescent probes or by assessing oxidative stress markers. The compound's effects on blood pressure and heart rate are monitored. Sample sizes typically range from 6-10 animals per group. P-1075 has also been used in models of neuroprotection and other conditions where KATP channels play a role. |
| ADME/Pharmacokinetics |
Molecular Weight: 231.30. Formula: C12H17N5. CAS No.: 60559-98-0. Synonyms: P-1075; P1075; PNU-83757; U-83757; N-cyano-N'-(1,1-dimethylpropyl)-N''-3-pyridinylguanidine. IUPAC Name: N-cyano-N'-(1,1-dimethylpropyl)-N''-3-pyridinylguanidine. Appearance: Solid. Purity: Typically ≥98%. Solubility: Soluble in DMSO. LogP: 2.10878. Polar Surface Area: 73.1 Ų. Rotatable Bonds: 3. Storage: Powder at -20°C for up to 3 years; 4°C for up to 2 years. Shipping: Room temperature. P-1075 is a potent and selective KATP channel activator with an EC50 of 45 nM. It is widely used in cardiovascular research to dissect KATP-mediated signal transduction and myocardial protection pathways.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available for P-1075. The compound is intended for research use only and has not undergone full preclinical toxicology evaluation required for clinical development. As a KATP channel activator, potential toxicities may include hypotension, tachycardia, and other cardiovascular effects due to vasodilation and reduced cardiac contractility. Standard toxicity studies would include acute toxicity assessment in rodents, repeated dose toxicity studies (14-day and 28-day), and genotoxicity screening (Ames test, micronucleus assay). The compound is for research use only and not for human therapeutic use.
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| References |
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| Additional Infomation |
1-Cyano-2-(2-methylbut-2-yl)-3-(3-pyridyl)guanidine is a member of the pyridine class of compounds.
P-1075 is also known as P1075, PNU-83757, U-83757, and N-cyano-N'-(1,1-dimethylpropyl)-N''-3-pyridinylguanidine. Its IUPAC name is N-cyano-N'-(1,1-dimethylpropyl)-N''-3-pyridinylguanidine. P-1075 is a potent and selective activator of SUR2-containing KATP channels with an EC50 of 45 nM. It is widely used in cardiovascular research to dissect KATP-mediated signal transduction, preconditioning mechanisms, and myocardial protection pathways. P-1075 is also used to evaluate KATP-targeted therapeutic strategies under ischemia-reperfusion and oxidative stress conditions. The compound produces reactive oxygen species by opening mitochondrial KATP channels, contributing to its cardioprotective effects. No clinical trials have been reported for this compound. P-1075 is for research use only. |
| Molecular Formula |
C12H17N5
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|---|---|
| Molecular Weight |
231.3
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| Exact Mass |
231.148
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| CAS # |
60559-98-0
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| PubChem CID |
43345
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| Appearance |
White to off-white solid powder
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| Density |
1.07g/cm3
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| Boiling Point |
347.6ºC at 760 mmHg
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| Melting Point |
186-187 °C
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| Flash Point |
164.1ºC
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| Index of Refraction |
1.556
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| LogP |
2.572
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
17
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| Complexity |
312
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
HKZNADVVGXKQDL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H17N5/c1-4-12(2,3)17-11(15-9-13)16-10-6-5-7-14-8-10/h5-8H,4H2,1-3H3,(H2,15,16,17)
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| Chemical Name |
1-cyano-2-(2-methylbutan-2-yl)-3-pyridin-3-ylguanidine
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| Synonyms |
U-83757; PNU-83757; P-1075
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~1080.85 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.99 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.99 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (8.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3234 mL | 21.6169 mL | 43.2339 mL | |
| 5 mM | 0.8647 mL | 4.3234 mL | 8.6468 mL | |
| 10 mM | 0.4323 mL | 2.1617 mL | 4.3234 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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