| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Target: NK1 receptor (neurokinin 1 receptor, also known as tachykinin receptor 1, TACR1). NK1 is a G protein-coupled receptor (GPCR) that binds the neuropeptide substance P. Activation of NK1 receptors is involved in pain transmission, inflammation, smooth muscle contraction, vasodilation, and emesis. L-760735 acts as a high-affinity NK1 receptor antagonist, blocking the binding of substance P and inhibiting downstream signaling pathways.
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| ln Vitro |
In vitro, L-760735 demonstrates high affinity for the NK1 receptor and antagonizes substance P-induced effects in various cell-based assays. Detailed IC50 and Ki values have not been disclosed in the public literature. The compound has been used in the synthetic preparation of (triazolylmethyl)morpholine derivatives as substance P antagonists. Further pharmacological characterization may be available in the patent literature.
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| ln Vivo |
No specific in vivo efficacy data have been published for L-760735. Based on its NK1 antagonist mechanism, related compounds have shown efficacy in animal models of emesis, pain, and anxiety. For NK1 antagonists, in vivo studies typically involve guinea pig models of emesis (substance P-induced or cisplatin-induced), rodent models of pain (formalin test, neuropathic pain models), and models of anxiety and depression (forced swim test, elevated plus maze). Detailed studies for L-760735 have not been reported.
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| Enzyme Assay |
For cell-free NK1 receptor binding assays: membranes prepared from cells expressing the human NK1 receptor (e.g., CHO-NK1 or U373MG cells) are incubated with varying concentrations of L-760735 (0-10 uM) and a radiolabeled NK1 antagonist tracer (e.g., 3H- or 125I-labeled substance P or high-affinity NK1 antagonist) in binding buffer (50 mM Tris-HCl pH 7.4, 5 mM MgCl2, 0.1% BSA) at room temperature for 60-90 min. Bound radioligand is separated by filtration and counted by scintillation. IC50 and Ki values are calculated from competition curves.
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| Cell Assay |
For cell-based assays: cells expressing the NK1 receptor (e.g., CHO-NK1 or U373MG glioblastoma cells) are seeded in 96-well plates and loaded with a calcium-sensitive dye (Fluo-4 AM, 2-5 uM, 60 min). Cells are pretreated with varying concentrations of L-760735 (0-10 uM) for 10-15 min, then stimulated with substance P (1-10 nM). Calcium flux is measured by fluorescence plate reader. IC50 for inhibition of substance P-induced calcium mobilization is calculated. For cAMP assays, cells are pretreated with L-760735, stimulated with substance P, and intracellular cAMP is measured by HTRF or AlphaScreen.
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| Animal Protocol |
No in vivo animal studies have been reported specifically for L-760735. A typical protocol for NK1 antagonist in vivo studies would involve male guinea pigs or gerbils. L-760735 would be administered intraperitoneally or orally at doses of 0.1-10 mg/kg 30-60 min before challenge. In emesis models, substance P (1-10 ug/kg) is injected intracerebroventricularly, and the number of retches and emetic episodes are recorded. In pain models, formalin (50 uL, 2.5%) is injected into the hind paw, and paw licking time is measured. L-760735 may also be used in models of anxiety and depression.
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| ADME/Pharmacokinetics |
PK properties of L-760735: For a small molecule NK1 antagonist (MW 611.98 as hydrochloride salt, solubility in DMSO <30.6 mg/mL), expected PK in rodents after oral administration: moderate oral bioavailability, Tmax 1-2 h, plasma half-life 4-8 h. The compound can be formulated in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline for IP administration or in 0.5% methylcellulose for oral gavage. The compound is stored at -20degC.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for L-760735. NK1 receptor antagonists are generally well-tolerated in preclinical and clinical studies. Common adverse effects of NK1 antagonists may include headache, fatigue, constipation, and dizziness. No specific toxicity studies for L-760735 have been published. The compound is for research use only and not for human consumption.
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| References | |
| Additional Infomation |
L-760735 is a research compound not yet approved for clinical use. It is a valuable tool for studying NK1 receptor biology and for developing substance P antagonists. NK1 antagonists have been clinically developed for emesis (aprepitant, fosaprepitant) and are approved by the FDA for chemotherapy-induced nausea and vomiting (CINV). Other NK1 antagonists have been investigated for depression, anxiety, and pain. L-760735 may be used as a reference standard in NK1 receptor antagonist research and in medicinal chemistry for lead optimization.
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| Molecular Formula |
C26H28N5O2F7.HCL
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|---|---|
| Molecular Weight |
611.98256
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| Exact Mass |
611.19
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| CAS # |
188923-01-5
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| PubChem CID |
9809076
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.46
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
41
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| Complexity |
774
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)O[C@@H]2[C@@H](N(CCO2)CC3=NNN=C3CN(C)C)C4=CC=C(C=C4)F.Cl
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| InChi Key |
VZBKOBSSEVXFNF-QIRDZIKRSA-N
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| InChi Code |
InChI=1S/C26H28F7N5O2.ClH/c1-15(17-10-18(25(28,29)30)12-19(11-17)26(31,32)33)40-24-23(16-4-6-20(27)7-5-16)38(8-9-39-24)14-22-21(13-37(2)3)34-36-35-22;/h4-7,10-12,15,23-24H,8-9,13-14H2,1-3H3,(H,34,35,36);1H/t15-,23+,24-;/m1./s1
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| Chemical Name |
1-[5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-2H-triazol-4-yl]-N,N-dimethylmethanamine;hydrochloride
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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 | 1.6340 mL | 8.1702 mL | 16.3404 mL | |
| 5 mM | 0.3268 mL | 1.6340 mL | 3.2681 mL | |
| 10 mM | 0.1634 mL | 0.8170 mL | 1.6340 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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