Synonym
Naloxegol Free Base; NKTR118; NKTR-118; NKTR 118; HSDB8338; HSDB-8338; HSDB 8338
IUPAC/Chemical Name
Morphinan-3,14-diol, 4,5-epoxy-6-(3,6,9,12,15,18,21-heptaoxadocos-1-yloxy)- 17-(2-propenyl)-, (5alpha,6alpha)-
InChi Key
XNKCCCKFOQNXKV-YZHZYEHBSA-N
InChi Code
InChI=1S/C34H53NO11/c1-3-9-35-10-8-33-30-26-4-5-27(36)31(30)46-32(33)28(6-7-34(33,37)29(35)25-26)45-24-23-44-22-21-43-20-19-42-18-17-41-16-15-40-14-13-39-12-11-38-2/h3-5,28-29,32,36-37H,1,6-25H2,2H3/t28-,29-,32+,33+,34-/m1/s1
SMILES Code
OC1=CC=C2C[C@@H](N(CC=C)CC3)[C@]4(O)CC[C@@H](OCCOCCOCCOCCOCCOCCOCCOC)[C@@]5([H])[C@]43C2=C1O5
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
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
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
Biological target:
Naloxegol Free Base is a peripherally acting opioid receptor antagonist specific for mu-opioid receptors.
In vitro activity:
At the human µ-opioid receptor in vitro, naloxegol was a potent inhibitor of binding (Ki = 7.42 nM) and a neutral competitive antagonist (pA2 - 7.95); agonist effects were <10% up to 30 μM and identical to those of naloxone.
Reference: J Pharmacol Exp Ther. 2017 May;361(2):280-291. https://pubmed.ncbi.nlm.nih.gov/28336575/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
651.79
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:
Floettmann E, Bui K, Sostek M, Payza K, Eldon M. Pharmacologic Profile of Naloxegol, a Peripherally Acting µ-Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation. J Pharmacol Exp Ther. 2017 May;361(2):280-291. doi: 10.1124/jpet.116.239061. Epub 2017 Mar 23. PMID: 28336575; PMCID: PMC5399635.
In vitro protocol:
Floettmann E, Bui K, Sostek M, Payza K, Eldon M. Pharmacologic Profile of Naloxegol, a Peripherally Acting µ-Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation. J Pharmacol Exp Ther. 2017 May;361(2):280-291. doi: 10.1124/jpet.116.239061. Epub 2017 Mar 23. PMID: 28336575; PMCID: PMC5399635.
1: Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014 Jun 19;370(25):2387-96. doi: 10.1056/NEJMoa1310246. Epub 2014 Jun 4. PMID: 24896818.
2: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Naloxegol. 2020 Mar 24. PMID: 31643924.
3: Daniali M, Nikfar S, Abdollahi M. Evaluating naloxegol for the treatment of opioid-induced constipation. Expert Opin Pharmacother. 2020 Jun;21(8):883-891. doi: 10.1080/14656566.2020.1735354. Epub 2020 Mar 4. PMID: 32129103.
4: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006–. Naloxegol. 2019 Jun 3. PMID: 31260226.
5: Bui K, Zhou D, Xu H, Floettmann E, Al-Huniti N. Clinical Pharmacokinetics and Pharmacodynamics of Naloxegol, a Peripherally Acting µ-Opioid Receptor Antagonist. Clin Pharmacokinet. 2017 Jun;56(6):573-582. doi: 10.1007/s40262-016-0479-z. PMID: 28035588.
6: Leppert W, Woron J. The role of naloxegol in the management of opioid-induced bowel dysfunction. Therap Adv Gastroenterol. 2016 Sep;9(5):736-46. doi: 10.1177/1756283X16648869. Epub 2016 May 26. PMID: 27582887; PMCID: PMC4984326.
7: Davies AN, Leach C. Naloxegol for opioid-induced sphincter of Oddi spasm/dysfunction. BMJ Support Palliat Care. 2019 Dec;9(4):365-366. doi: 10.1136/bmjspcare-2019-001808. Epub 2019 Jun 14. PMID: 31201151.
8: Al-Huniti N, Zhou D, Xu H, Aksenov S, Bui KH, Fox R, Helmlinger G, Stanski D. Pharmacometric Modeling of Naloxegol Efficacy and Safety: Impact on Dose and Label. Clin Pharmacol Ther. 2017 Nov;102(5):741-744. doi: 10.1002/cpt.719. Epub 2017 May 26. PMID: 28548207.
9: ▼Naloxegol for opioid-induced constipation. Drug Ther Bull. 2015 Dec;53(12):138-40. doi: 10.1136/dtb.2015.12.0369. PMID: 26660436.
10: Tack J, Corsetti M. Naloxegol for the treatment of opioid-induced constipation. Expert Rev Gastroenterol Hepatol. 2014 Nov;8(8):855-61. doi: 10.1586/17474124.2014.939629. Epub 2014 Sep 15. PMID: 25220391.
