NCX-4016
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MedKoo CAT#: 532313

CAS#: 175033-36-0

Description: NCX-4016 is a nitroderivative of aspirin that combines cyclooxygenase inhibitor with an NO donor. NCX 4016 improves postischemic ventricular dysfunction and to reduce myocardial infarct size in rabbit. NCX-4016 is an NO-NSAID type compound.

Chemical Structure

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NCX-4016
CAS# 175033-36-0
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 532313
Name: NCX-4016
CAS#: 175033-36-0
Chemical Formula: C16H13NO7
Exact Mass: 331.07
Molecular Weight: 331.280
Elemental Analysis: C, 58.01; H, 3.96; N, 4.23; O, 33.81

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25mg USD 430
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Synonym: NCX-4016; NCX 4016; NCX4016.

IUPAC/Chemical Name: [3-(nitrooxymethyl)phenyl] 2-acetyloxybenzoate

InChi Key: IOJUJUOXKXMJNF-UHFFFAOYSA-N

InChi Code: InChI=1S/C16H13NO7/c1-11(18)23-15-8-3-2-7-14(15)16(19)24-13-6-4-5-12(9-13)10-22-17(20)21/h2-9H,10H2,1H3

SMILES Code: O=C(OC1=CC=CC(CO[N+]([O-])=O)=C1)C2=CC=CC=C2OC(C)=O

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

More Info:

Product Data:
Product Data
Instruction:
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Biological target: NCX-4016 is a nitroderivative of aspirin that combines cyclooxygenase inhibitor with an NO donor.
In vitro activity: Dialysis experiments showed that oCOX-1 inhibition by NCX 4016, similar to aspirin, is irreversible. Reversible COX inhibitors (indomethacin) or salicylic acid incubated with the enzyme before NCX 4016 prevent the irreversible inhibition of oCOX-1 by NCX 4016 as well as by aspirin. In conclusion, these data show that NCX 4016 acts as a direct and irreversible inhibitor of COX-1 and that the presence of a spacer and NO-donating moiety in the molecule slows the kinetics of COX-1 inhibition by NCX 4016, compared with aspirin. Reference: J Pharmacol Exp Ther. 2005 Dec;315(3):1331-7. https://pubmed.ncbi.nlm.nih.gov/16144976/
In vivo activity: Hamsters were treated with NCX-4016 (100 mg/kg or 30 mg.kg(-1).day(-1) for 5 days po) or DETA-NO (0.5 mg/kg). Mean arterial blood pressure increased slightly but significantly after NCX-4016 treatment. During 5- and 15-min reperfusion, lipid peroxides in the systemic blood increased by 72 and 89% vs. baseline, respectively, and were still higher than in basal conditions after 30-min reperfusion in the I/R group. Pretreatment with NCX-4016 maintained ROS at normal levels; increased arteriolar diameter, blood flow, and PCL; and decreased leukocyte adhesion (P < 0.05). Reference: Am J Physiol Gastrointest Liver Physiol. 2004 Mar;286(3):G437-43. https://pubmed.ncbi.nlm.nih.gov/14563672/

Preparing Stock Solutions

The following data is based on the product molecular weight 331.28 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.

Recalculate based on batch purity %
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. Selvendiran K, Bratasz A, Tong L, Ignarro LJ, Kuppusamy P. NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and modulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts. Cell Cycle. 2008 Jan 1;7(1):81-8. doi: 10.4161/cc.7.1.5103. Epub 2007 Sep 28. PMID: 18196976; PMCID: PMC2890223. 2. Corazzi T, Leone M, Maucci R, Corazzi L, Gresele P. Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016). J Pharmacol Exp Ther. 2005 Dec;315(3):1331-7. doi: 10.1124/jpet.105.089896. Epub 2005 Sep 6. PMID: 16144976. 3. Rambotti MG, Mariucci G, Tantucci M, Ambrosini MV. Ultracytochemical demonstration of soluble guanylate cyclase activation in rat aorta by NCX4016, a NO-releasing aspirin derivative. J Submicrosc Cytol Pathol. 2006 Jun-Sep;38(2-3):149-54. PMID: 17784643. 4. Bertuglia S, Giusti A, Del Soldato P. Antioxidant activity of nitro derivative of aspirin against ischemia-reperfusion in hamster cheek pouch microcirculation. Am J Physiol Gastrointest Liver Physiol. 2004 Mar;286(3):G437-43. doi: 10.1152/ajpgi.00339.2003. Epub 2003 Oct 16. PMID: 14563672.
In vitro protocol: 1. Selvendiran K, Bratasz A, Tong L, Ignarro LJ, Kuppusamy P. NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and modulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts. Cell Cycle. 2008 Jan 1;7(1):81-8. doi: 10.4161/cc.7.1.5103. Epub 2007 Sep 28. PMID: 18196976; PMCID: PMC2890223. 2. Corazzi T, Leone M, Maucci R, Corazzi L, Gresele P. Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016). J Pharmacol Exp Ther. 2005 Dec;315(3):1331-7. doi: 10.1124/jpet.105.089896. Epub 2005 Sep 6. PMID: 16144976.
In vivo protocol: 1. Rambotti MG, Mariucci G, Tantucci M, Ambrosini MV. Ultracytochemical demonstration of soluble guanylate cyclase activation in rat aorta by NCX4016, a NO-releasing aspirin derivative. J Submicrosc Cytol Pathol. 2006 Jun-Sep;38(2-3):149-54. PMID: 17784643. 2. Bertuglia S, Giusti A, Del Soldato P. Antioxidant activity of nitro derivative of aspirin against ischemia-reperfusion in hamster cheek pouch microcirculation. Am J Physiol Gastrointest Liver Physiol. 2004 Mar;286(3):G437-43. doi: 10.1152/ajpgi.00339.2003. Epub 2003 Oct 16. PMID: 14563672.

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1: Ulu N, Iskit AB, Sökmensüer C, Güç MO. The effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on mice models of endotoxic and septic shock. Turk J Med Sci. 2015;45(4):812-9. PubMed PMID: 26422851.

2: Derhaschnig U, Schweeger-Exeli I, Marsik C, Cardona F, Minuz P, Jilma B. Effects of aspirin and NO-aspirin (NCX 4016) on platelet function and coagulation in human endotoxemia. Platelets. 2010;21(5):320-8. doi: 10.3109/09537101003735572. PubMed PMID: 20608787.

3: Expression of concern. NCX-4016 (NO-aspirin) inhibits lipopolysaccharide-induced tissue factor expression in vivo: role of nitric oxide. Circulation. 2009 Mar 17;119(10):e367. doi: 10.1161/CIRCULATIONAHA.109.192170. PubMed PMID: 19289646.

4: Kaddai V, Gonzalez T, Bolla M, Le Marchand-Brustel Y, Cormont M. The nitric oxide-donating derivative of acetylsalicylic acid, NCX 4016, stimulates glucose transport and glucose transporters translocation in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab. 2008 Jul;295(1):E162-9. doi: 10.1152/ajpendo.00622.2007. Epub 2008 May 20. PubMed PMID: 18492771.

5: Huizinga TW. NCX-4016 NicOx SA. IDrugs. 1998 Jun;1(2):228-31. PubMed PMID: 18465536.

6: Selvendiran K, Bratasz A, Tong L, Ignarro LJ, Kuppusamy P. NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and modulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts. Cell Cycle. 2008 Jan 1;7(1):81-8. Epub 2007 Sep 28. PubMed PMID: 18196976; PubMed Central PMCID: PMC2890223.

7: Wan S, Shukla N, Angelini GD, Yim AP, Johnson JL, Jeremy JY. Nitric oxide-donating aspirin (NCX 4016) inhibits neointimal thickening in a pig model of saphenous vein-carotid artery interposition grafting: a comparison with aspirin and morpholinosydnonimine (SIN-1). J Thorac Cardiovasc Surg. 2007 Oct;134(4):1033-9. PubMed PMID: 17903525.

8: Parinandi NL, Sharma A, Eubank TD, Kaufman BF, Kutala VK, Marsh CB, Ignarro LJ, Kuppusamy P. Nitroaspirin (NCX-4016), an NO donor, is antiangiogenic through induction of loss of redox-dependent viability and cytoskeletal reorganization in endothelial cells. Antioxid Redox Signal. 2007 Nov;9(11):1837-49. PubMed PMID: 17760507.

9: Gresele P, Migliacci R, Procacci A, De Monte P, Bonizzoni E. Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication. Thromb Haemost. 2007 Mar;97(3):444-50. PubMed PMID: 17334512.

10: Kutala VK, Khan M, Mandal R, Potaraju V, Colantuono G, Kumbala D, Kuppusamy P. Prevention of postischemic myocardial reperfusion injury by the combined treatment of NCX-4016 and Tempol. J Cardiovasc Pharmacol. 2006 Sep;48(3):79-87. PubMed PMID: 17031260.

11: Gresele P, Momi S. Pharmacologic profile and therapeutic potential of NCX 4016, a nitric oxide-releasing aspirin, for cardiovascular disorders. Cardiovasc Drug Rev. 2006 Summer;24(2):148-68. Review. PubMed PMID: 16961726.

12: Bratasz A, Weir NM, Parinandi NL, Zweier JL, Sridhar R, Ignarro LJ, Kuppusamy P. Reversal to cisplatin sensitivity in recurrent human ovarian cancer cells by NCX-4016, a nitro derivative of aspirin. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3914-9. Epub 2006 Feb 23. PubMed PMID: 16497833; PubMed Central PMCID: PMC1450164.

13: Ambrosini MV, Mariucci G, Rambotti MG, Tantucci M, Covarelli C, De Angelis L, Del Soldato P. Ultrastructural investigations on protective effects of NCX 4016 (nitroaspirin) on macrovascular endothelium in diabetic Wistar rats. J Submicrosc Cytol Pathol. 2005 Aug;37(2):205-13. PubMed PMID: 16335593.

14: Corazzi T, Leone M, Maucci R, Corazzi L, Gresele P. Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016). J Pharmacol Exp Ther. 2005 Dec;315(3):1331-7. Epub 2005 Sep 6. PubMed PMID: 16144976.

15: Fiorucci S, Mencarelli A, Meneguzzi A, Lechi A, Renga B, del Soldato P, Morelli A, Minuz P. Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans. J Am Coll Cardiol. 2004 Aug 4;44(3):635-41. PubMed PMID: 15358033.

16: Emanueli C, Van Linthout S, Salis MB, Monopoli A, Del Soldato P, Ongini E, Madeddu P. Nitric oxide-releasing aspirin derivative, NCX 4016, promotes reparative angiogenesis and prevents apoptosis and oxidative stress in a mouse model of peripheral ischemia. Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):2082-7. Epub 2004 Sep 2. PubMed PMID: 15345513.

17: Carini M, Aldini G, Orioli M, Piccoli A, Rossoni G, Maffei Facino R. Nitric oxide release and distribution following oral and intraperitoneal administration of nitroaspirin (NCX 4016) in the rat. Life Sci. 2004 May 14;74(26):3291-305. PubMed PMID: 15094329.

18: Carini M, Aldini G, Orioli M, Piccoli A, Tocchetti P, Facino RM. Chemiluminescence and LC-MS/MS analyses for the study of nitric oxide release and distribution following oral administration of nitroaspirin (NCX 4016) in healthy volunteers. J Pharm Biomed Anal. 2004 Apr 16;35(2):277-87. PubMed PMID: 15063462.

19: Fiorucci S, Distrutti E, Mencarelli A, Rizzo G, Lorenzo AR, Baldoni M, Del Soldato P, Morelli A, Wallace JL. Cooperation between aspirin-triggered lipoxin and nitric oxide (NO) mediates antiadhesive properties of 2-(Acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester (NCX-4016) (NO-aspirin) on neutrophil-endothelial cell adherence. J Pharmacol Exp Ther. 2004 Jun;309(3):1174-82. Epub 2004 Feb 4. PubMed PMID: 14762100.

20: Mann NS. No-Aspirin (NCX 4016). Gastroenterology. 2003 Dec;125(6):1918-9. PubMed PMID: 14727635.