P-1075 | CAS#60559-98-0 | K-ATP channel agonist

MedKoo Cat#: 529713 | Name: P-1075

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

P-1075, also known as PNU-83757 and U-83757, is a K-ATP channel agonist potentially for the treatment of erectile dysfunction, alopecia and arrhythmia.

Chemical Structure

P-1075

CAS#60559-98-0

Theoretical Analysis

MedKoo Cat#: 529713

Name: P-1075

CAS#: 60559-98-0

Chemical Formula: C12H17N5

Exact Mass: 231.1484

Molecular Weight: 231.30

Elemental Analysis: C, 62.31; H, 7.41; N, 30.28

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 330.00
50mg	USD 990.00

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Synonym

P-1075; PNU-83757; U-83757; P1075; PNU83757; U83757; P 1075; PNU 83757; U 83757

IUPAC/Chemical Name

N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine

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)

SMILES Code

CCC(N/C(NC#N)=N/C1=CC=CN=C1)(C)C

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

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

P-1075 is a potent activator of sulfonylurea receptor 2-associated ATP-sensitive potassium channels (SUR2-KIR6).

In vitro activity:

This study next tested whether P1075 causes rabbit cardiomyocytes to produce ROS in a K(ATP)-dependent fashion. Mitochondrial ROS production was monitored by the appearance of fluorescence as reduced MitoTracker Red was oxidized. P1075 (100 microM) led to a 44 +/- 9% increase in ROS generation (P < 0.001 vs. untreated cells), which was similar to the increase seen with 50 microM diazoxide, a selective mitoK(ATP) channel opener (49 +/- 9%, P < 0.001 vs. untreated cells). Reference: J Mol Cell Cardiol. 2003 Sep;35(9):1035-42. https://pubmed.ncbi.nlm.nih.gov/12967626/

In vivo activity:

P1075 induced a concentration-dependent relaxation of rat renal artery rings pre-contracted by phenylephrine. Glibenclamide, a selective K(ATP) channels inhibitor, partly antagonized the relaxation of rat renal artery induced by P1075. Tetraethylammonium (TEA), a non-selective inhibitor of Ca(2+)-activated K(+) channels, as well as iberiotoxin, a most selective blocker of large-conductance Ca(2+) -activated K(+) (BK(Ca)) channels, did not abolish the effect of P1075 on rat renal artery. Reference: Basic Clin Pharmacol Toxicol. 2012 Jul;111(1):24-30. https://pubmed.ncbi.nlm.nih.gov/22225832/

	Solvent	mg/mL	mM
Solubility
	DMSO	250.0	1,080.83

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 231.30 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.

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. Oldenburg O, Yang XM, Krieg T, Garlid KD, Cohen MV, Grover GJ, Downey JM. 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. doi: 10.1016/s0022-2828(03)00151-2. PMID: 12967626. 2. Löffler-Walz C, Hambrock A, Quast U. Interaction of K(ATP) channel modulators with sulfonylurea receptor SUR2B: implication for tetramer formation and allosteric coupling of subunits. Mol Pharmacol. 2002 Feb;61(2):407-14. doi: 10.1124/mol.61.2.407. PMID: 11809866. 3. Novakovic A, Pavlovic M, Milojevic P, Stojanovic I, Nenezic D, Jovic M, Ugresic N, Kanjuh V, Yang Q, He GW. Different potassium channels are involved in relaxation of rat renal artery induced by P1075. Basic Clin Pharmacol Toxicol. 2012 Jul;111(1):24-30. doi: 10.1111/j.1742-7843.2011.00855.x. Epub 2012 Jan 20. PMID: 22225832. 4. Gojkovic-Bukarica LC, Beleslin-Cokic BB, Novakovic AN, Peric MS, Markovic-Lipkovski JZ, Cirovic SZ, Nezic DG, Lesic AR, Kanjuh VI, Heinle H. The effects of potassium channel opener P1075 on the human saphenous vein and human internal mammary artery. J Cardiovasc Pharmacol. 2011 Jun;57(6):648-55. doi: 10.1097/FJC.0b013e3182145850. PMID: 21346595.

In vitro protocol:

In vivo protocol:

1. Novakovic A, Pavlovic M, Milojevic P, Stojanovic I, Nenezic D, Jovic M, Ugresic N, Kanjuh V, Yang Q, He GW. Different potassium channels are involved in relaxation of rat renal artery induced by P1075. Basic Clin Pharmacol Toxicol. 2012 Jul;111(1):24-30. doi: 10.1111/j.1742-7843.2011.00855.x. Epub 2012 Jan 20. PMID: 22225832. 2. Gojkovic-Bukarica LC, Beleslin-Cokic BB, Novakovic AN, Peric MS, Markovic-Lipkovski JZ, Cirovic SZ, Nezic DG, Lesic AR, Kanjuh VI, Heinle H. The effects of potassium channel opener P1075 on the human saphenous vein and human internal mammary artery. J Cardiovasc Pharmacol. 2011 Jun;57(6):648-55. doi: 10.1097/FJC.0b013e3182145850. PMID: 21346595.

1: Dyhring T, Jansen-Olesen I, Christophersen P, Olesen J. Pharmacological Profiling of KATP Channel Modulators: An Outlook for New Treatment Opportunities for Migraine. Pharmaceuticals (Basel). 2023 Feb 1;16(2):225. doi: 10.3390/ph16020225. PMID: 37259373; PMCID: PMC9966414. 2: Zhang X, Zhang X, Xiong Y, Xu C, Liu X, Lin J, Mu G, Xu S, Liu W. Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis. Int J Mol Med. 2016 Sep;38(3):758-66. doi: 10.3892/ijmm.2016.2664. Epub 2016 Jul 5. PMID: 27430376; PMCID: PMC4990318. 3: Protić D, Beleslin-Čokić B, Spremović-Rađenović S, Radunović N, Heinle H, Sćepanović R, Gojković Bukarica L. The different effects of resveratrol and naringenin on isolated human umbilical vein: the role of ATP-sensitive K⁺ channels. Phytother Res. 2014 Sep;28(9):1412-8. doi: 10.1002/ptr.5145. Epub 2014 Mar 17. PMID: 24638940. 4: Novakovic A, Pavlovic M, Milojevic P, Stojanovic I, Nenezic D, Jovic M, Ugresic N, Kanjuh V, Yang Q, He GW. Different potassium channels are involved in relaxation of rat renal artery induced by P1075. Basic Clin Pharmacol Toxicol. 2012 Jul;111(1):24-30. doi: 10.1111/j.1742-7843.2011.00855.x. Epub 2012 Jan 20. PMID: 22225832. 5: Chowdhury UR, Bahler CK, Hann CR, Chang M, Resch ZT, Romero MF, Fautsch MP. ATP-sensitive potassium (KATP) channel activation decreases intraocular pressure in the anterior chamber of the eye. Invest Ophthalmol Vis Sci. 2011 Aug 16;52(9):6435-42. doi: 10.1167/iovs.11-7523. PMID: 21743021; PMCID: PMC3176023. 6: Gojkovic-Bukarica LC, Beleslin-Cokic BB, Novakovic AN, Peric MS, Markovic- Lipkovski JZ, Cirovic SZ, Nezic DG, Lesic AR, Kanjuh VI, Heinle H. The effects of potassium channel opener P1075 on the human saphenous vein and human internal mammary artery. J Cardiovasc Pharmacol. 2011 Jun;57(6):648-55. doi: 10.1097/FJC.0b013e3182145850. PMID: 21346595. 7: Amann T, Schell S, Kühner P, Winkler M, Schwanstecher M, Russ U, Quast U. Substitution of the Walker A lysine by arginine in the nucleotide-binding domains of sulphonylurea receptor SUR2B: effects on ligand binding and channel activity. Naunyn Schmiedebergs Arch Pharmacol. 2010 Jun;381(6):507-16. doi: 10.1007/s00210-010-0510-0. Epub 2010 Mar 30. PMID: 20352196. 8: Ploug KB, Sørensen MA, Strøbech L, Klaerke DA, Hay-Schmidt A, Sheykhzade M, Olesen J, Jansen-Olesen I. K ATP channels in pig and human intracranial arteries. Eur J Pharmacol. 2008 Dec 28;601(1-3):43-9. doi: 10.1016/j.ejphar.2008.10.041. Epub 2008 Oct 29. PMID: 18996111. 9: Jilkina O, Kuzio B, Kupriyanov VV. Potassium fluxes, energy metabolism, and oxygenation in intact diabetic rat hearts under normal and stress conditions. Can J Physiol Pharmacol. 2008 Oct;86(10):710-25. doi: 10.1139/y08-076. PMID: 18841176. 10: Ng B, Kang Y, Xie H, Sun H, Gaisano HY. Syntaxin-1A inhibition of P-1075, cromakalim, and diazoxide actions on mouse cardiac ATP-sensitive potassium channel. Cardiovasc Res. 2008 Dec 1;80(3):365-74. doi: 10.1093/cvr/cvn210. Epub 2008 Aug 14. PMID: 18703534. 11: Dupuis JP, Revilloud J, Moreau CJ, Vivaudou M. Three C-terminal residues from the sulphonylurea receptor contribute to the functional coupling between the K(ATP) channel subunits SUR2A and Kir6.2. J Physiol. 2008 Jul 1;586(13):3075-85. doi: 10.1113/jphysiol.2008.152744. Epub 2008 May 1. PMID: 18450778; PMCID: PMC2538783. 12: Ploug KB, Boni LJ, Baun M, Hay-Schmidt A, Olesen J, Jansen-Olesen I. K(ATP) channel expression and pharmacological in vivo and in vitro studies of the K(ATP) channel blocker PNU-37883A in rat middle meningeal arteries. Br J Pharmacol. 2008 May;154(1):72-81. doi: 10.1038/bjp.2008.86. Epub 2008 Mar 10. PMID: 18332850; PMCID: PMC2438990. 13: Miragoli M, Salvarani N, Rohr S. Myofibroblasts induce ectopic activity in cardiac tissue. Circ Res. 2007 Oct 12;101(8):755-8. doi: 10.1161/CIRCRESAHA.107.160549. Epub 2007 Sep 13. Erratum in: Circ Res. 2007 Nov 9;101(10):e114. PMID: 17872460. 14: Gross ER, Hsu AK, Gross GJ. GSK3beta inhibition and K(ATP) channel opening mediate acute opioid-induced cardioprotection at reperfusion. Basic Res Cardiol. 2007 Jul;102(4):341-9. doi: 10.1007/s00395-007-0651-6. Epub 2007 Apr 23. PMID: 17450314. 15: Sato T, Nakaya H. P-1075 exerts diverse modulatory effects on mitochondrial ATP-sensitive K+ channels in rabbit ventricular myocytes. J Cardiovasc Pharmacol. 2006 Feb;47(2):165-8. doi: 10.1097/01.fjc.0000199224.40799.a4. PMID: 16495751. 16: Milicic I, Buckner SA, Daza A, Coghlan M, Fey TA, Brune ME, Gopalakrishnan M. Pharmacological characterization of urinary bladder smooth muscle contractility following partial bladder outlet obstruction in pigs. Eur J Pharmacol. 2006 Feb 17;532(1-2):107-14. doi: 10.1016/j.ejphar.2005.12.076. Epub 2006 Feb 17. PMID: 16487510. 17: Jansen-Olesen I, Mortensen CH, El-Bariaki N, Ploug KB. Characterization of K(ATP)-channels in rat basilar and middle cerebral arteries: studies of vasomotor responses and mRNA expression. Eur J Pharmacol. 2005 Oct 31;523(1-3):109-18. doi: 10.1016/j.ejphar.2005.08.028. Epub 2005 Oct 13. PMID: 16226739. 18: Moses MA, Addison PD, Neligan PC, Ashrafpour H, Huang N, McAllister SE, Lipa JE, Forrest CR, Pang CY. Inducing late phase of infarct protection in skeletal muscle by remote preconditioning: efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1609-17. doi: 10.1152/ajpregu.00395.2005. Epub 2005 Sep 22. PMID: 16179491. 19: Bozdogan O, Gonca E, Nebigil M, Tiryaki ES. Effect of thimerosal on arrhythmia induced by coronary ligation: the involvement of ATP-dependent potassium channels. Int Heart J. 2005 Jul;46(4):711-21. doi: 10.1536/ihj.46.711. Erratum in: Int Heart J. 2024;65(2):372. doi: 10.1536/ihj.65-2_Errata. PMID: 16157962. 20: Rainbow RD, Norman RI, Hudman D, Davies NW, Standen NB. Reduced effectiveness of HMR 1098 in blocking cardiac sarcolemmal K(ATP) channels during metabolic stress. J Mol Cell Cardiol. 2005 Oct;39(4):637-46. doi: 10.1016/j.yjmcc.2005.06.017. PMID: 16099467.