P-1075 is a potent activator of sulfonylurea receptor 2-related ATP-sensitive potassium channels (SUR2-KIR6) with EC50 of 45 nM. P-1075 can also protect the heart in rabbits by opening mitochondrial K (ATP) channels to produce reactive oxygen species.

Physicochemical Properties

Molecular Formula	C12H17N5
Molecular Weight	231.3
Exact Mass	231.148
CAS #	60559-98-0
PubChem CID	43345
Appearance	White to off-white solid powder
Density	1.07g/cm3
Boiling Point	347.6ºC at 760 mmHg
Melting Point	186-187 °C
Flash Point	164.1ºC
Index of Refraction	1.556
LogP	2.572
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	17
Complexity	312
Defined Atom Stereocenter Count	0
InChi Key	HKZNADVVGXKQDL-UHFFFAOYSA-N
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)
Chemical Name	1-cyano-2-(2-methylbutan-2-yl)-3-pyridin-3-ylguanidine
Synonyms	U-83757; PNU-83757; P-1075
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
ln Vivo	In ischemia models, P1075 (iv; 1 μg/kg; once) therapy resulted in a smaller infarct [3].
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).
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.
References	[1]. Potassium channel openers require ATP to bind to and act through sulfonylurea receptors. EMBO J. 1998 Oct 1;17(19):5529-35. [2]. P1075 opens mitochondrial K(ATP) channels and generates reactive oxygen species resulting in cardioprotection of rabbit hearts. J Mol Cell Cardiol. 2003 Sep;35(9):1035-42. [3]. GSK3beta inhibition and K(ATP) channel opening mediate acute opioid-induced cardioprotection at reperfusion. Basic Res Cardiol. 2007 Jul;102(4):341-9.
Additional Infomation	1-cyano-2-(2-methylbutan-2-yl)-3-(3-pyridinyl)guanidine is a member of pyridines.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~1080.85 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.