Naldemedine
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MedKoo CAT#: 326729

CAS#: 916072-89-4 (free base)

Description: Naldemedine, also known as S 297995, is a peripherally-selective μ-opioid receptor antagonist under development by Shionogi for the treatment of opioid-induced adverse effects including constipation, nausea, and vomiting. Clinical studies have thus far found it to possess statistically significant effectiveness for these indications and to be generally well-tolerated with predominantly mild to moderate gastrointestinal side effects. No effects indicative of central opioid withdrawal or impact on the analgesic or mydriatic effects of co-administered opioids have been observed.


Price and Availability

Size Price Shipping out time Quantity
2mg USD 1950 2 Weeks
5mg USD 3950 2 Weeks
Inquire bulk and customized quantity

Pricing updated 2020-09-22. Prices are subject to change without notice.

Naldemedine, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 326729
Name: Naldemedine
CAS#: 916072-89-4 (free base)
Chemical Formula: C32H34N4O6
Exact Mass: 570.2478
Molecular Weight: 570.646
Elemental Analysis: C, 67.35; H, 6.01; N, 9.82; O, 16.82


Related CAS #: 1345728-04-2 (tosylate)   916072-89-4 (free base)    

Synonym: S 297995; S-297995; S297995; S 297,995; S-297,995; S297,995; Naldemedine; Symproic;

IUPAC/Chemical Name: 17-(cyclopropylmethyl)-6,7-didehydro-4,5alpha-epoxy-3,6,14-trihydroxy-N-(2-(3-phenyl- 1,2,4-oxadiazol-5-yl)propan-2-yl)morphinan-7-carboxamide

InChi Key: AXQACEQYCPKDMV-PFMBVUTNSA-N

InChi Code: InChI=1S/C32H34N4O6/c1-30(2,29-33-27(35-42-29)18-6-4-3-5-7-18)34-28(39)20-15-32(40)22-14-19-10-11-21(37)25-23(19)31(32,26(41-25)24(20)38)12-13-36(22)16-17-8-9-17/h3-7,10-11,17,22,26,37-38,40H,8-9,12-16H2,1-2H3,(H,34,39)/t22-,26-,31+,32-/m1/s1

SMILES Code: O=C(C1=C(O)[C@@H]2[C@]34C5=C(O2)C(O)=CC=C5C[C@@H](N(CC6CC6)CC4)[C@]3(O)C1)NC(C)(C7=NC(C8=CC=CC=C8)=NO7)C


Technical Data

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, not in water

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


References

1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548373/ PubMed PMID: 31643694.

2: Ishii K, Yamashita H, Yamaguchi M, Komatsu Y, Ryu E, Morishita S, Matsuo K, Kamada M, Ikeda T, Ashizawa K, Hara T. Naldemedine-induced Opioid Withdrawal Syndrome in a Patient with Breast Cancer without Brain Metastasis: A Case Report. Intern Med. 2019 Sep 18. doi: 10.2169/internalmedicine.3098-19. [Epub ahead of print] PubMed PMID: 31534081.

3: Osaka I, Ishiki H, Yokota T, Tada Y, Sato H, Okamoto M, Satomi E. Safety and efficacy of naldemedine in cancer patients with opioid-induced constipation: a pooled, subgroup analysis of two randomised controlled studies. ESMO Open. 2019 Jul 31;4(4):e000527. doi: 10.1136/esmoopen-2019-000527. eCollection 2019. PubMed PMID: 31423335; PubMed Central PMCID: PMC6677965.

4: Blair HA. Naldemedine: A Review in Opioid-Induced Constipation. Drugs. 2019 Jul;79(11):1241-1247. doi: 10.1007/s40265-019-01160-7. Review. PubMed PMID: 31267482.

5: Sato J, Tanaka R, Ishikawa H, Suzuki T, Shino M. A preliminary study of the effect of naldemedine tosylate on opioid-induced nausea and vomiting. Support Care Cancer. 2019 Jun 11. doi: 10.1007/s00520-019-04884-0. [Epub ahead of print] PubMed PMID: 31183560.

6: Wild J, Yamada T, Arjona Ferreira JC, Hale M. Onset of action of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: results from 2 randomized, placebo-controlled, phase 3 trials. Pain. 2019 Oct;160(10):2358-2364. doi: 10.1097/j.pain.0000000000001629. PubMed PMID: 31145214; PubMed Central PMCID: PMC6756260.

7: Fukumura K, Yamada T, Yokota T, Kawasaki A. The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Naldemedine. Clin Pharmacol Drug Dev. 2019 Apr 12. doi: 10.1002/cpdd.690. [Epub ahead of print] PubMed PMID: 30977959.

8: Esmadi M, Ahmad D, Hewlett A. Efficacy of naldemedine for the treatment of opioid-induced constipation: A meta-analysis. J Gastrointestin Liver Dis. 2019 Mar;28(1):41-46. doi: 10.15403/jgld.2014.1121.281.any. PubMed PMID: 30851171.

9: Kanemasa T, Koike K, Arai T, Ono H, Horita N, Chiba H, Nakamura A, Morioka Y, Kihara T, Hasegawa M. Pharmacologic effects of naldemedine, a peripherally acting μ-opioid receptor antagonist, in in vitro and in vivo models of opioid-induced constipation. Neurogastroenterol Motil. 2019 May;31(5):e13563. doi: 10.1111/nmo.13563. Epub 2019 Feb 28. PubMed PMID: 30821019; PubMed Central PMCID: PMC6850587.

10: Watari R, Matsuda A, Ohnishi S, Hasegawa H. Minimal contribution of P-gp on the low brain distribution of naldemedine, a peripherally acting μ-opioid receptor antagonist. Drug Metab Pharmacokinet. 2019 Apr;34(2):126-133. doi: 10.1016/j.dmpk.2018.12.002. Epub 2018 Dec 23. PubMed PMID: 30770183.

11: Song X, Wang D, Qu X, Dong N, Teng S. A meta-analysis of naldemedine for the treatment of opioid-induced constipation. Expert Rev Clin Pharmacol. 2019 Feb;12(2):121-128. doi: 10.1080/17512433.2019.1570845. Epub 2019 Jan 24. Review. PubMed PMID: 30652502.

12: Saito Y, Yokota T, Arai M, Tada Y, Sumitani M. Naldemedine in Japanese patients with opioid-induced constipation and chronic noncancer pain: open-label Phase III studies. J Pain Res. 2018 Dec 24;12:127-138. doi: 10.2147/JPR.S175900. eCollection 2019. PubMed PMID: 30613161; PubMed Central PMCID: PMC6307491.

13: Inagaki M, Kume M, Tamura Y, Hara S, Goto Y, Haga N, Hasegawa T, Nakamura T, Koike K, Oonishi S, Kanemasa T, Kai H. Discovery of naldemedine: A potent and orally available opioid receptor antagonist for treatment of opioid-induced adverse effects. Bioorg Med Chem Lett. 2019 Jan 1;29(1):73-77. doi: 10.1016/j.bmcl.2018.11.007. Epub 2018 Nov 7. PubMed PMID: 30446313.

14: Ohnishi S, Fukumura K, Kubota R, Wajima T. Absorption, distribution, metabolism, and excretion of radiolabeled naldemedine in healthy subjects. Xenobiotica. 2019 Sep;49(9):1044-1053. doi: 10.1080/00498254.2018.1536815. Epub 2019 Jan 4. PubMed PMID: 30351180.

15: Kubota R, Fukumura K, Wajima T. Population Pharmacokinetics and Exposure-Response Relationships of Naldemedine. Pharm Res. 2018 Oct 2;35(11):225. doi: 10.1007/s11095-018-2501-7. PubMed PMID: 30280262; PubMed Central PMCID: PMC6182381.

16: Hu K, Bridgeman MB. Naldemedine (Symproic) for the Treatment Of Opioid-Induced Constipation. P T. 2018 Oct;43(10):601-627. PubMed PMID: 30271103; PubMed Central PMCID: PMC6152697.

17: Shikada Y, Emi Y, Kometani T, Ochiai T, Fujii M, Noda Y, Kajiwara M, Ikeda M, Asonuma S, Mori M. [A New Twist on the Administration of Naldemedine for Opioid-Induced Constipation in an Outpatient]. Gan To Kagaku Ryoho. 2018 Jul;45(7):1075-1079. Japanese. PubMed PMID: 30042276.

18: Katakami N, Harada T, Murata T, Shinozaki K, Tsutsumi M, Yokota T, Arai M, Tada Y, Narabayashi M, Boku N. Randomized phase 3 and extension studies: Efficacy and impacts on quality of life of naldemedine in subjects with opioid-induced constipation and cancer. Ann Oncol. 2018 Apr 18. doi: 10.1093/annonc/mdy118. [Epub ahead of print] PubMed PMID: 29912271; PubMed Central PMCID: PMC6005145.

19: Webster LR, Nalamachu S, Morlion B, Reddy J, Baba Y, Yamada T, Arjona Ferreira JC. Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study. Pain. 2018 May;159(5):987-994. doi: 10.1097/j.pain.0000000000001174. PubMed PMID: 29419653; PubMed Central PMCID: PMC5916485.

20: Yagi Y, Kosugi K, Tanimoto T. Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer. J Clin Oncol. 2018 Apr 1;36(10):1049-1050. doi: 10.1200/JCO.2017.76.9349. Epub 2018 Feb 6. PubMed PMID: 29406801.