| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Other Sizes |
Purity: ≥98%
| Targets |
Naloxegol acts as a competitive antagonist at μ‑, δ‑, and κ‑opioid receptors. Binding affinity (Ki): μ‑opioid receptor: 4.8 ng/mL; κ‑opioid receptor: 5.6 ng/mL; δ‑opioid receptor: 132 ng/mL. It shows ~1.2‑fold higher affinity for μ‑ versus κ‑receptors, and ~27‑fold higher affinity for μ‑ versus δ‑receptors.
[1] |
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| ln Vitro |
Naloxegol demonstrates high binding affinity to μ‑ and κ‑opioid receptors with Ki values as above. It has a morphinan ring‑based structure with a covalently bound PEG chain that reduces blood‑brain barrier penetration and makes it a substrate for P‑glycoprotein efflux transporter. In rat perfusion studies, the rate of brain entry was 4.1 pmol/g brain/s, significantly slower than naloxone (60.2 pmol/g brain/s), similar to atenolol (5.17 pmol/g brain/s), which does not cross the blood‑brain barrier. Quantitative whole‑body autoradiography in rats showed that radioactivity concentrations in brain and spinal cord were 30‑fold lower than in serum. At therapeutic dosing, Naloxegol antagonizes μ‑opioid receptors for 15 hours. No clinically relevant accumulation occurs between day 1 and day 28 with daily dosing of 5, 25, and 50 mg. It does not affect metabolic enzymes or transporters at therapeutic concentrations.
[1] |
| ln Vivo |
In vivo efficacy was demonstrated in phase II and III clinical trials (KODIAC‑04, ‑05) in patients with non‑cancer pain and OIC. In the phase II study, 25 mg and 50 mg doses significantly increased median change from baseline in spontaneous bowel movements (SBMs) per week at week 1 (25 mg: 2.9 vs placebo 1.0, P=0.002; 50 mg: 3.3 vs 0.5, P=0.0001). Time to first laxation was shorter for 25 mg (6.6 vs 48.6 h, P=0.0012) and 50 mg (2.9 vs 44.9 h, P=0.0016). In KODIAC‑04 and ‑05, the 25 mg dose was superior to placebo in the primary endpoint (≥3 SBMs/week and increase ≥1 from baseline for ≥9 of 12 weeks and ≥3 of final 4 weeks) in intention‑to‑treat populations (K4: 44% vs 29.4%, P=0.001; K5: 39.7% vs 29.3%, P=0.02) and laxative nonresponder populations (K4: 48.7% vs 28.8%, P=0.002; K5: 46.8% vs 31.4%, P=0.01). The 12.5 mg dose was superior in K4 only. Both doses shortened time to first laxation. Pain scores and daily opioid doses remained stable across studies, with no clinically significant changes, indicating preservation of central analgesia. In the long‑term safety study (KODIAC‑08, 52 weeks), adverse events were mostly mild to moderate and occurred primarily within the first 12 weeks.
[1] |
| Animal Protocol |
In rat perfusion studies, the rate of brain entry for Naloxegol was measured at 4.1 pmol/g brain/s, compared to naloxone at 60.2 pmol/g brain/s and atenolol at 5.17 pmol/g brain/s. A quantitative whole‑body autoradiography study in rats showed that radioactivity concentrations of Naloxegol in brain and spinal cord were 30‑fold lower than in serum. These experiments were performed to assess blood‑brain barrier penetration. No further details on animal protocols (e.g., dosing formulation, route) are provided in the article.
[1] |
| ADME/Pharmacokinetics |
Naloxegol pharmacokinetics: At therapeutic dosing of 25 mg daily, it antagonizes μ‑opioid receptors for 15 hours. Maximum plasma concentration (Cmax) is achieved in <2 hours after single doses from 5 to 1000 mg. A secondary peak occurs 0.4‑3 hours after the first peak in most patients. Steady state is reached within 2‑3 days. Mean terminal elimination half‑life (t1/2) is 10 hours at 12.5 and 25 mg doses. Dose‑proportional pharmacokinetics (Cmax and AUC increase proportionally with dose). Absolute bioavailability in humans not determined. Administration with food increases AUC by 54% and Cmax by 41% (when taken 0.5 h before breakfast); therefore, fasting administration is recommended. Age, gender, ethnicity, body weight, prior laxative response, and baseline opioid dose have minimal impact on pharmacokinetics. Metabolism: primarily via CYP3A4 and biliary excretion; renal route minor (67.7% in feces, 16% in urine). Enterohepatic recycling occurs (suggested by bimodal AUC). Major circulating species is parent drug; major metabolic pathway (1/3 of dose) involves PEG chain cleavage, oxidation, and dealkylation; six metabolites each ≤10% of parent, all retain reduced CNS penetration. In renal impairment: moderate (GFR 30‑59 mL/min/1.73m²) increases AUC 1.7‑fold, Cmax 1.1‑fold; severe (GFR <30) increases AUC 2.2‑fold, Cmax 1.8‑fold; ESRD on hemodialysis shows similar AUC but 29% lower Cmax. Lower starting dose recommended for moderate/severe renal impairment. Hepatic impairment: mild (Child‑Pugh A) and moderate (B) decrease AUC by 17‑18% with similar Cmax; t1/2 decreased (mild 9.6 h, moderate 7.5 h vs healthy 11.3 h); no dose adjustment for mild/moderate, but use not recommended in severe (Child‑Pugh C).
[1] |
| Toxicity/Toxicokinetics |
Naloxegol adverse events: In the phase III KODIAC‑08 long‑term safety study (52 weeks), overall adverse events occurred in 81.8% with Naloxegol 25 mg vs 72.2% with usual care; serious adverse events similar (9.6% vs 11.1%). Common adverse events included abdominal pain (17.8% vs 3.3%), diarrhea (12.9% vs 5.9%), nausea (9.4% vs 4.1%), headache (9% vs 4.8%), flatulence (6.9% vs 1.1%), and upper abdominal pain (5.1% vs 1.1%). Discontinuation due to adverse events occurred in 10.5% of Naloxegol patients. Most GI events were mild‑to‑moderate and resolved during or after discontinuation. Cardiac repolarization: A phase I crossover study in healthy males showed that at therapeutic (25 mg) and supratherapeutic (150 mg) doses, mean increase in QTc was <5 ms and all upper 90% CI limits <10 ms at all time points; no clinically relevant effect on cardiac repolarization. Drug interactions: Coadministration with strong/moderate CYP3A4 and P‑glycoprotein inhibitors increases Naloxegol exposure (strong inhibitors ~10‑fold, moderate 2‑ to 5‑fold); strong CYP3A4 inducers decrease exposure. Examples provided. Caution advised with these drugs. No QT/QTc prolongation at therapeutic dose.
[1] |
| References | |
| Additional Infomation |
See also: Naloxixol (with active ingredient).
Drug Indications For the treatment of opioid-induced constipation (OIC) in adult patients with an inadequate response to laxatives. Naloxegol is indicated for opioid‑induced constipation in adult patients with chronic non‑cancer pain. It is a PEGylated derivative of naloxone that acts peripherally, with minimal CNS penetration due to P‑glycoprotein efflux and low intrinsic permeability. At therapeutic doses, it does not reverse central analgesia, as shown by stable pain scores and lack of opioid withdrawal (except transient GI component at 50 mg). Recommended starting dose: 25 mg once daily on an empty stomach (≥1 h before or 2 h after first meal); reduce to 12.5 mg if not tolerated. For renal impairment (CrCl <60 mL/min), start at 12.5 mg once daily; may escalate if tolerated. Contraindicated in known or suspected GI obstruction. Avoid in severe hepatic impairment. Cost: US$299.52 for 30 tablets (12.5 or 25 mg) as of 2015. It is effective in laxative‑refractory patients, but further studies are needed to compare with methylnaltrexone and traditional laxatives. It may improve patient adherence to opioid therapy and quality of life. [1] |
| Molecular Formula |
C36H55NO15
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|---|---|
| Molecular Weight |
741.828
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| Exact Mass |
741.357
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| CAS # |
1354744-91-4
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| Related CAS # |
1354744-91-4 (oxalate) 854601-70-0
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| PubChem CID |
56959086
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| Appearance |
White to off-white solid powder
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| LogP |
0.957
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
25
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| Heavy Atom Count |
52
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| Complexity |
971
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O[C@@]1(CC[C@H](OCCOCCOCCOCCOCCOCCOCCOC)[C@]2([H])OC3=C4O)[C@]52C3=C(C=C4)C[C@@]1([H])N(CC=C)CC5.OC(C(O)=O)=O
|
| InChi Key |
(4R,4aS,7S,7aR,12bS)-7-((2,5,8,11,14,17,20-heptaoxadocosan-22-yl)oxy)-3-allyl-1,2,3,4,5,6,7,7a-octahydro-4aH-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol oxalate
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| InChi Code |
MNYIRXLCPODKLG-VUTNLTPYSA-N SMILES
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| Chemical Name |
NKTR-118 AZ-13337019NKTR 118 AZ 13337019NKTR118 AZ13337019 EGylated naloxol Naloxegol Oxalate trade names Movantik and Moventig.
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| Synonyms |
Related CAS #
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3480 mL | 6.7401 mL | 13.4802 mL | |
| 5 mM | 0.2696 mL | 1.3480 mL | 2.6960 mL | |
| 10 mM | 0.1348 mL | 0.6740 mL | 1.3480 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01623609 | COMPLETED | Drug: Naloxegol Drug: Naloxegol |
Opioid Induced Constipation | AstraZeneca | 2012-07 | Phase 1 |
| NCT04219046 | UNKNOWN STATUS | Drug: Naloxégol oxalate Drug: Placebo oral tablet |
Bladder Cancer Cystostomy; Complications |
Institut Paoli-Calmettes | 2021-03 | Phase 2 |
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