| Size | Price | Stock | Qty |
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| Targets |
κ-opioid receptor (KOR), with antagonistic activity also observed at μOR (IC50 = 110 nM) and δOR (IC50 = 6500 nM). Navacaprant is a selective KOR antagonist with an IC50 of 0.8 nM for κOR, displaying >100-fold selectivity over MOR and DOR. It inhibits the signaling pathway between G-protein-coupled receptors (GPCRs) and G proteins.
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| ln Vitro |
At Kappa opioid receptors, navacaprant (BTRX-335140) (0-10 μM; 4 hours) demonstrates selective antagonist action [1].
Navacaprant demonstrates selective antagonist activity against the κ-opioid receptor at concentrations ranging from 0-10 μM. In cell-based functional assays, it exhibits potent antagonism at KOR with an IC50 of 0.8 nM, while showing significantly weaker activity at μOR (IC50 = 110 nM) and δOR (IC50 = 6500 nM). The compound penetrates well into the CNS, making it suitable for neuropathy and CNS disorder research. |
| ln Vivo |
Navacaprant (BTRX-335140) (0.01-3 mg/kg; once oral) lowers plasma prolactin secretion triggered by U69,593 to levels not induced by U69,593 [1]. When administered intraperitoneally, navacaprant (BTRX-335140) (1 mg/kg) inhibits the analgesic action of hot water due to U-50488 [1]. 1.19 BTRX-335140 pharmacokinetic properties in rodents [1]. AUC0-t (h• ng/mL) 153 725 265 232 Vss (L/kg) 13.8 7.72 F (%) 30.2 12 Rat IV 1 mg/kg, Mouse IV 3 mg/kg, Rat PO 5 mg/kg, and Mouse PO 10 mg/kg CL (mL/min/kg) 105 66.5 t1/2 (h) 1.81 1.91 6.19 2.57
Navacaprant (0.01-3 mg/kg; p.o., once) decreases U69,593-stimulated plasma prolactin secretion to levels equivalent to those without U69,593 treatment. At 1 mg/kg (i.p., once), it inhibits U-50488-induced antinociception in response to hot water. The compound shows a medication-like duration of action in rats, supporting its potential for once-daily oral dosing. |
| Enzyme Assay |
In vitro receptor binding assays for Navacaprant involve measuring its affinity for κ-opioid, μ-opioid, and δ-opioid receptors using radioligand displacement techniques. Membranes from cells expressing the respective receptors are incubated with a radiolabeled opioid ligand and increasing concentrations of Navacaprant. Bound and free ligand are separated by filtration, and radioactivity is measured by scintillation counting. IC50 values are determined from competition binding curves using nonlinear regression analysis.
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| Cell Assay |
Cell viability assay [1]
Cell Types: OPRK1-BLA U2OS Cell Tested Concentrations: 0-10 μM Incubation Duration: 4 hrs (hours) Experimental Results: demonstrated antagonistic activity against KOR, DOR and MOR, with IC50 values of 0.8, 110 and 6500 nM respectively, and Displays selective antagonistic activity of KOR. Cellular assays for Navacaprant typically utilize cell lines expressing κ-opioid receptors to measure antagonist activity. Cells are treated with various concentrations of Navacaprant (0-10 μM) and stimulated with a KOR agonist. Receptor-mediated signaling, such as G protein activation or downstream effector modulation, is measured. The compound's ability to inhibit agonist-induced responses is assessed, confirming its potent and selective KOR antagonism. |
| Animal Protocol |
Animal/Disease Models: Rat PRL model [1]
Doses: 0.01, 0.03, 0.1, 0.3, 1 and 3 mg /kg Route of Administration: po (oral gavage); 0.01-3 mg/kg Primary Experimental Results:Even at a dose of 0.1 mg/kg, it can effectively reduce the high level of prolactin caused by U69,593. Animal/Disease Models: Adult male ICR mice, tail immersed in 50°C hot water [1] Doses: 1 mg/kg Route of Administration: intraperitoneal (ip) injection; 1 mg/kg Primary Experimental Results:Resistance during 1 hour instead of 24 hrs (hrs (hours)) of pretreatment blocked U-50488-induced analgesia and demonstrated drug-like duration of action in blocking KOR. In vivo animal studies for Navacaprant typically involve administration to rodent models via oral or intraperitoneal routes. Efficacy is assessed by measuring the compound's ability to block KOR agonist-induced effects, such as prolactin secretion or antinociception. Pharmacokinetic parameters are determined from serial blood sampling. The compound's duration of action and CNS penetration are evaluated, supporting its investigation for neuropsychiatric disorders. |
| ADME/Pharmacokinetics |
Navacaprant possesses favorable in vitro ADMET and in vivo pharmacokinetic profiles with a medication-like duration of action in rats. It penetrates well into the CNS and is orally active. The compound's pharmacokinetic profile supports once-daily oral dosing. Further detailed pharmacokinetic parameters such as half-life, bioavailability, and clearance have been characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have established a favorable safety profile for Navacaprant. The compound is well tolerated at doses that produce pharmacodynamic effects. No significant adverse events have been reported in preclinical studies. The compound's selectivity for KOR over other opioid receptors contributes to its favorable safety profile. Comprehensive toxicological evaluation has been conducted to support its progression into clinical development.
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| References | |
| Additional Infomation |
BTRX-335140 is being studied in the clinical trial NCT04221230 (BTRX-335140 vs. placebo for major depressive disorder).
Navacaprant (BTRX-335140, formerly CYM-53093) is a selective and orally active κ-opioid receptor (KOR) antagonist that has been investigated for the treatment of neuropsychiatric and neurodegenerative disorders. Its mechanism of action involves potent and selective KOR antagonism, which modulates dopaminergic and stress-related pathways. The compound has been evaluated in preclinical and early clinical studies for depression, substance use disorders, and neuropathy. Its favorable pharmacokinetic and safety profiles support its continued development as a potential therapeutic agent. |
| Molecular Formula |
C25H32FN5O2
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| Molecular Weight |
453.552289009094
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| Exact Mass |
453.254
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| CAS # |
2244614-14-8
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| PubChem CID |
137434175
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
630
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=CC(CC)=CC2=C1N=C(C(C1=NC(C)=NO1)=C2C)N1CCC(CC1)NC1CCOCC1
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| InChi Key |
CQOJHAJWCDJEAT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H32FN5O2/c1-4-17-13-20-15(2)22(25-27-16(3)30-33-25)24(29-23(20)21(26)14-17)31-9-5-18(6-10-31)28-19-7-11-32-12-8-19/h13-14,18-19,28H,4-12H2,1-3H3
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| Chemical Name |
1-[6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)quinolin-2-yl]-N-(oxan-4-yl)piperidin-4-amine
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| Synonyms |
BTRX335140; BTRX 335140; BTRX-335140
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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 : ~3.85 mg/mL (~8.49 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.68 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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 1 mg/mL (2.20 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.20 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2048 mL | 11.0241 mL | 22.0483 mL | |
| 5 mM | 0.4410 mL | 2.2048 mL | 4.4097 mL | |
| 10 mM | 0.2205 mL | 1.1024 mL | 2.2048 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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