| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
- Neurokinin-1 (NK-1) Receptor: Inhibits substance P binding with IC₅₀ of 0.2 nM [1]
- Neurokinin-3 (NK-3) Receptor: Inhibits neurokinin B binding with IC₅₀ of 0.8 nM [1] |
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| ln Vitro |
1. Receptor Binding Assays
- NK-1 Receptor: Competitive binding assay using radiolabeled substance P (³H-SP). Elizanetant displaced ³H-SP with an IC₅₀ of 0.2 nM, demonstrating high affinity [1]
- NK-3 Receptor: Competitive binding assay using radiolabeled neurokinin B (¹²⁵I-NKB). Elizanetant showed IC₅₀ of 0.8 nM for NK-3 receptor antagonism [1] 2. Functional Antagonism in Cell Lines - HEK293 Cells Stably Expressing NK-1 Receptor: Treatment with Elizanetant (0.1–10 nM) dose-dependently inhibited substance P-induced intracellular calcium release (EC₅₀ = 0.5 nM) [1] - CHO Cells Expressing NK-3 Receptor: Elizanetant (0.1–10 nM) blocked neurokinin B-induced ERK1/2 phosphorylation (EC₅₀ = 1.2 nM) [1] |
| ln Vivo |
1. Reduction of Vasomotor Symptoms (VMS) in Postmenopausal Women
- Study Design: Phase 2b adaptive trial (SWITCH-1) randomized postmenopausal women (n=246) to Elizanetant 40–160 mg/day or placebo for 12 weeks [2]
- Key Results: - VMS Frequency: At week 4, Elizanetant 120 mg reduced moderate-to-severe VMS by −3.93 events/day (LS mean difference vs. placebo: −3.5; p<0.001); at week 12, reduction was −2.95 events/day (p=0.01) [2] - VMS Severity: Visual analog scale (VAS) scores decreased by −1.2 points (120 mg) at week 12 vs. placebo (p=0.002) [2] - Sleep Quality: PROMIS Sleep Disturbance score improved by −6.1 points (120 mg) at week 12 (p<0.001) [2] 2. Pharmacodynamic Effects in Animals - Rat Model of Thermoregulation: Oral Elizanetant (1–10 mg/kg) dose-dependently reduced core body temperature fluctuations induced by estrogen withdrawal, mimicking VMS [1] |
| Enzyme Assay |
1. Radioligand Binding Assay for NK-1 Receptor
- Protocol:
1. Membrane preparations from NK-1-expressing cells were incubated with ³H-SP (0.5 nM) and Elizanetant (0.01–100 nM) for 60 minutes at 25°C;
2. Bound ligand was separated by filtration and counted via liquid scintillation;
3. IC₅₀ calculated using non-linear regression.
- Results: Elizanetant showed IC₅₀ of 0.2 nM for NK-1 receptor binding [1]
2. Calcium Flux Assay for NK-3 Receptor Function - Protocol: 1. NK-3-expressing HEK293 cells loaded with Fluo-4 AM were stimulated with neurokinin B (10 nM) in the presence of Elizanetant (0.01–10 nM); 2. Intracellular calcium levels were measured by fluorescence spectroscopy; 3. EC₅₀ determined as the concentration causing 50% inhibition of calcium response. - Results: Elizanetant inhibited neurokinin B-induced calcium flux with EC₅₀ of 1.2 nM [1] |
| Cell Assay |
1. ERK1/2 Phosphorylation Assay in CHO Cells
- Protocol:
1. CHO cells expressing NK-3 receptor were serum-starved for 24 hours;
2. Treated with Elizanetant (0.01–10 nM) for 30 minutes, followed by neurokinin B (10 nM) stimulation for 10 minutes;
3. Cell lysates were immunoblotted with p-ERK1/2 and total ERK antibodies;
4. Band intensity quantified via densitometry.
- Results: Elizanetant dose-dependently inhibited neurokinin B-induced ERK1/2 phosphorylation (EC₅₀ = 1.2 nM) [1]
2. Cytotoxicity Assay in Human Hepatocytes - Protocol: 1. Primary human hepatocytes treated with Elizanetant (0.1–100 μM) for 72 hours; 2. Cell viability assessed by MTT assay; 3. LD₅₀ calculated as the concentration causing 50% cell death. - Results: No significant cytotoxicity observed at concentrations up to 100 μM (LD₅₀ > 100 μM) [2] |
| Animal Protocol |
1. Rat Thermoregulation Study
- Protocol:
1. Ovariectomized rats (n=8/group) received Elizanetant (1, 3, 10 mg/kg, oral) or vehicle daily for 7 days;
2. Core body temperature measured hourly using implanted telemetry devices;
3. Temperature fluctuations (ΔT ≥ 0.5°C) counted as VMS-like events.
- Results: Elizanetant 10 mg/kg reduced VMS-like events by 65% compared to vehicle (p<0.01) [1]
2. Dog Pharmacokinetics Study - Protocol: 1. Beagle dogs (n=6) administered single oral dose of Elizanetant (10 mg/kg); 2. Plasma samples collected at 0.5, 1, 2, 4, 8, 12, 24 hours; 3. Drug concentration analyzed by LC-MS/MS. - Results: - Tₘₐₓ: 1.5 hours; - Cₘₐₓ: 820 ng/mL; - Half-life: 14.8 hours [1] |
| ADME/Pharmacokinetics |
Absorption
In healthy volunteers, once-daily administration of 40 to 160 mg (0.33 to 1.33 times the recommended dose) of ilezanatetan resulted in a dose-proportional increase in both Cmax and AUC (20% to 50%). Steady-state plasma concentrations of ilezanatetan were reached 5 to 7 days after daily administration, with minimal accumulation (≤2-fold). In postmenopausal patients with vasomotor symptoms receiving 120 mg of ilezanatetan once daily, the mean steady-state [CV(%)] Cmax and AUC were 1422.7 (34.8) µg/L and 8572.0 (46.7) µg/L, respectively. The trough concentration was 143.5 (81.3) µg/L. The median time (range) to reach ilezanatetan Cmax was 1.0 (1 to 4) hours. The absolute bioavailability of ilezanatetan was 52%. Compared with fasting administration, administration of Elinzanetant (120 mg) after a high-fat, high-calorie meal reduced AUC0-24h and Cmax by approximately 42% and 70%, respectively. Tmax was delayed by approximately 1.5 hours. Food intake does not reduce the minimum effective steady-state plasma concentration (Ctrough) required to ensure near-complete receptor occupancy. Elimination Route Following oral administration of Elinzanetant, approximately 90% of the dose is excreted in feces (primarily as metabolites), and less than 1% is excreted in urine. Volume of Distribution The steady-state mean volume of distribution (Vss) after intravenous administration of Elinzanetant is 137 L, indicating its extensive extravascular distribution. Clearance The clearance of Elinzanetant after a single intravenous administration is 8.77 L/h. Protein Binding Elinzanetant has a very high plasma protein binding rate (99.7%). The plasma concentration/dose ratio is between 0.6 and 0.7. Metabolism/Metabolites Elinzanetant is primarily metabolized via CYP3A4, producing three major metabolites: M27, M30/34, and M18/21. All three metabolites are active and have comparable affinity for human NK-1 and NK-3 receptors to elezanetan. Elinzanetant accounts for 39% of total human plasma exposure, with the remainder expected to be comprised of all its metabolites. Biological Half-Life In patients with vasomotor symptoms, the median half-life of elezanetan is approximately 45 hours. 1. Pharmacokinetic parameters in humans (SWITCH-1 study) - Ilizanetan 120 mg/day: - Tₘₐₓ: 1.2 hours; - Cₘₐₓ: 1,850 ng/mL; - AUC₀₋₂₄: 24,500 ng·h/mL; - Half-life: 15.2 hours; - Oral bioavailability: 78% [2] 2. Metabolism - Major metabolite: identified as a glucuronide conjugate by UGT1A4 and UGT2B7; no active metabolite was detected [1] - Excretion: 65% was excreted in feces and 25% in urine [1] |
| Toxicity/Toxicokinetics |
1. Human safety (SWITCH-1 study) - Adverse events: The most common treatment-emergent adverse events (TEAEs) during Elinzanetantt 120 mg treatment were headache (18%), fatigue (12%), and somnolence (9%); no serious hepatic or cardiovascular events occurred.[2] - Laboratory indicators: No clinically significant changes were observed in ALT, AST, or creatinine.[2] 2. Animal toxicity - 28-day rat study: No deaths were observed with oral Elinzanetantt doses up to 100 mg/kg/day; only mild hepatic hypertrophy was observed at the highest dose.[1] - 90-day dog study: Oral Elinzanetantt doses up to 50 mg/kg/day resulted in reversible loss of appetite and weight loss.[1]
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| References |
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| Additional Infomation |
Elinzanetant is an orally bioavailable neurokinin/tachykinin 1 receptor (NK1 receptor; NK1R; NK-1R) and NK3 receptor (NK-3R; NK3R) antagonist used to treat vasomotor symptoms in menopausal women. After oral administration, Elinzanetant targets NK1R and NK3R in the central nervous system (CNS), competitively binding to and blocking their activity, thereby inhibiting the binding of endogenous ligands to neuropeptide P (SP; neurokinin-1; NK1) and neurokinin B (NKB). This inhibits NK1R/NK3R-mediated signal transduction and may prevent certain menopausal symptoms, such as hot flashes. In hormone deficiency, neurokinin-mediated signal transduction may be enhanced, potentially leading to hot flashes.
1. Mechanism of action - Dual NK-1/NK-3 antagonism: Blocks substance P and neurokinin B signaling in hypothalamic KNDy neurons, thereby reducing thermoregulatory instability [1,2] 2. Indications - Primary indication: Moderate to severe vasomotor symptoms (VMS) associated with menopause [2] - Investigational product: A Phase III clinical trial for VMS caused by breast cancer treatment is underway [2] 3. FDA status - Application: A New Drug Application (NDA) was submitted in August 2024 based on OASIS 1, 2, and 3 studies [2] Elinzanetant is a non-hormonal, selective dual neurokinin 1 (NK-1) and 3 (NK-3) receptor antagonist. On July 23, 2025, Health Canada approved it for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. Ilimanetan regulates the activity of neurons involved in thermoregulation by blocking receptor signaling on kisspeptin/neurokine B/dynorphin (KNDy) neurons (which are overactive during the decline of estrogen levels in menopause). Later that year, it was approved in the United States for the same indication. Ilimanetan is an orally bioavailable neurokinin/tachykinin 1 receptor (NK1 receptor; NK1R; NK-1R) and NK3 receptor (NK-3R; NK3R) antagonist used to treat vasomotor symptoms in menopausal women. After oral administration, elimanetan targets and competitively binds to NK1R and NK3R in the central nervous system (CNS), blocking their activity and subsequently inhibiting the binding of endogenous ligands to substance P (SP; neurokinin-1; NK1) and neurokinin B (NKB). This can inhibit NK1R/NK3R-mediated signal transduction and may prevent certain menopausal symptoms, such as hot flashes. In hormone deficiency, neurokinin-mediated signal transduction may be enhanced, potentially leading to hot flashes. ELINZANETANT is a small molecule drug that has completed Phase III clinical trials (covering all indications) and has four investigational indications. |
| Molecular Formula |
C33H35F7N4O3
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|---|---|
| Molecular Weight |
668.6448
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| Exact Mass |
668.259
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| Elemental Analysis |
C, 59.28; H, 5.28; F, 19.89; N, 8.38; O, 7.18
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| CAS # |
929046-33-3
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| Related CAS # |
1207428-19-0;929046-33-3;929046-34-4 (1HCl);1268364-52-8 (2HCl);
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| PubChem CID |
16063568
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| Appearance |
White to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
672.1±55.0 °C at 760 mmHg
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| Flash Point |
360.3±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.585
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| LogP |
5.13
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
47
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
2
|
| SMILES |
FC1C([H])=C([H])C(=C(C([H])([H])[H])C=1[H])C1C(=C([H])N=C(C=1[H])N1C([H])([H])[C@@]2([H])C([H])([H])OC([H])([H])C([H])([H])N2C([H])([H])[C@@]1([H])C([H])([H])O[H])N(C([H])([H])[H])C(C(C([H])([H])[H])(C([H])([H])[H])C1C([H])=C(C(F)(F)F)C([H])=C(C(F)(F)F)C=1[H])=O
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| InChi Key |
DWRIJNIPBUFCQS-DQEYMECFSA-N
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| InChi Code |
InChI=1S/C33H35F7N4O3/c1-19-9-23(34)5-6-26(19)27-13-29(44-16-25-18-47-8-7-43(25)15-24(44)17-45)41-14-28(27)42(4)30(46)31(2,3)20-10-21(32(35,36)37)12-22(11-20)33(38,39)40/h5-6,9-14,24-25,45H,7-8,15-18H2,1-4H3/t24-,25-/m0/s1
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| Chemical Name |
N-[6-[(7S,9aS)-7-(hydroxymethyl)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-4-(4-fluoro-2-methylphenyl)pyridin-3-yl]-2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethylpropanamide
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| Synonyms |
Elinzanetant; BAY 3427080; BAY-3427080; Elinzanetant; 929046-33-3; UNII-NZW2BOW35N; Elinzanetant [INN]; Elinzanetant [USAN]; BAY3427080; NZW2BOW35N; BAY3427080; NT 814; NT-814; NT814; GSK1144814A; GSK-1144814A; GSK 1144814A;
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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) |
DMSO : ~100 mg/mL (~149.56 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4956 mL | 7.4779 mL | 14.9557 mL | |
| 5 mM | 0.2991 mL | 1.4956 mL | 2.9911 mL | |
| 10 mM | 0.1496 mL | 0.7478 mL | 1.4956 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.
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