| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
L-365260 targets the cholecystokinin B receptor (CCK-B/CCK2), a G protein-coupled receptor that is activated by the neuropeptide cholecystokinin (CCK) and gastrin. It acts as a competitive antagonist, binding to the receptor with high affinity. L-365260 has Ki values of 1.9 nM for gastrin receptors and 2.0 nM for brain CCK receptors. The compound is orally active and selective for CCK-B over CCK-A receptors.
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| ln Vitro |
In many neurons, CCK8S- and CCK4-mediated depolarization is significantly attenuated by L-365260 (1 μM) [2]. For CCK-B receptors in the brains of rats, mice, and humans, L-365260 demonstrates a comparable high affinity, whereas its affinity for gastrin and brain CCK-B (IC50=20–40 nM) receptors in dog tissue is lower[1].
In vitro, L-365260 selectively binds to CCK-B receptors with high affinity (Ki = 1.9 nM for gastrin receptors and 2.0 nM for CCK-B receptors). The compound inhibits CCK-induced signaling in cells expressing CCK-B receptors, as measured by calcium mobilization or other downstream signaling readouts. L-365260 has been shown to inhibit the proliferation of thyroid carcinoma (TT) cells, suggesting potential therapeutic implications for cancer treatment. |
| ln Vivo |
Rats given submaximal doses of morphine (4 mg/kg) experience analgesia that is potentiated by L-365260 (0.01-10 mg/kg; subcutaneous injection) [3]. In rats, the duration of morphine analgesia was greatly extended by L-365260 (0.2 mg/kg; subcutaneous injection twice daily for 5 days) [3]. Gastrin enhancement of acid secretion in mice (ED50=0.03 mg/kg), rats (ED50=0.9 mg/kg), and guinea pigs (ED50=5.1 mg/kg) is antagonized by L-365260 (0.1-30 mg/kg; po)[1].
In vivo, L-365260 enhances amphetamine-induced stimulation of locomotor activity in rats, a model of drug abuse. It also enhances morphine analgesia and prevents morphine tolerance. Bilateral injection of L-365260 into the medulla reverses both tactile allodynia and thermal hyperalgesia in pain models. These findings indicate that L-365260 modulates CCK-B receptor-mediated effects on pain, reward, and drug-seeking behavior. |
| Enzyme Assay |
The non-cellular assay for L-365260 involves measuring its binding affinity for CCK-B receptors using radioligand binding assays. Membrane preparations from tissues or cells expressing CCK-B receptors are incubated with a radiolabeled CCK-B ligand (such as [¹²⁵I]-CCK-8 or [³H]-pentagastrin) and varying concentrations of L-365260. The inhibition of radioligand binding is measured, and the Ki is determined from competition curves.
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| Cell Assay |
The cellular assay for L-365260 involves treating cells expressing CCK-B receptors with the compound and measuring its effects on receptor-mediated signaling. Cells are loaded with a calcium-sensitive dye, and the increase in intracellular calcium in response to CCK stimulation is measured using fluorescence microscopy or a plate reader. L-365260 is added prior to CCK stimulation, and the inhibition of the calcium response is measured. The IC50 is determined from concentration-response curves.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (300-350 g) injected with morphine [3]
Doses: 0.01, 0.05, 0.1, 0.2, 0.75, 1.0, 10.0 mg/kg Route of Administration: 10 minutes before subcutaneous injection 4 mg/kg Morphine Experimental Results: The analgesic effect of morphine is enhanced. In the in vivo efficacy study, L-365260 is administered orally or by injection to rodent models. In the morphine analgesia study, mice or rats are treated with L-365260 prior to morphine administration, and analgesic effects are measured using the hot plate test or tail flick test. In the drug abuse model, L-365260 is administered prior to amphetamine, and locomotor activity is measured. In pain models, the compound is injected into the medulla, and tactile allodynia and thermal hyperalgesia are assessed. |
| ADME/Pharmacokinetics |
L-365260 has a molecular weight of 398.46 and a molecular formula of C₂₄H₂₂N₄O₂. The compound is orally active. It should be stored as a powder at -20°C, protected from light and moisture. The compound is stable when stored properly and should be handled with appropriate laboratory safety precautions.
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| Toxicity/Toxicokinetics |
The toxicological profile of L-365260 has not been extensively characterized in the published literature. As a CCK-B antagonist, it may have effects on gastrointestinal function, pain perception, and behavior. Comprehensive toxicology data are limited, and L-365260 is not approved for clinical use. The compound should be handled with appropriate laboratory safety precautions.
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| References |
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| Additional Infomation |
L-365260 is a benzodiazepine drug.
L-365260 is a selective CCK-B receptor antagonist that has been widely used as a research tool to study the role of CCK-B receptors in pain, reward, and gastrointestinal function. It has been shown to enhance morphine analgesia and prevent morphine tolerance, suggesting potential applications in pain management. The compound has also been studied for its effects on drug abuse and cancer cell proliferation. L-365260 is not approved for clinical use and is strictly a research compound. |
| Molecular Formula |
C24H22N4O2
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|---|---|
| Molecular Weight |
398.47
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| Exact Mass |
398.174
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| CAS # |
118101-09-0
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| Related CAS # |
L-365260 hemihydrate
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| PubChem CID |
5311201
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| Appearance |
White to off-white solid powder
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| Density |
1.23g/cm3
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| Boiling Point |
611.5ºC at 760 mmHg
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| Flash Point |
323.6ºC
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| Vapour Pressure |
6.85E-15mmHg at 25°C
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| Index of Refraction |
1.648
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| LogP |
3.921
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
658
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC(=CC=C1)NC(=O)N[C@H]2C(=O)N(C3=CC=CC=C3C(=N2)C4=CC=CC=C4)C
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| InChi Key |
KDFQABSFVYLGPM-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C24H22N4O2/c1-16-9-8-12-18(15-16)25-24(30)27-22-23(29)28(2)20-14-7-6-13-19(20)21(26-22)17-10-4-3-5-11-17/h3-15,22H,1-2H3,(H2,25,27,30)/t22-/m0/s1
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| Chemical Name |
1-[(3R)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea
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| Synonyms |
L365260; L 365260; L-365260
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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 (~250.97 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.27 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 (6.27 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 | 2.5096 mL | 12.5480 mL | 25.0960 mL | |
| 5 mM | 0.5019 mL | 2.5096 mL | 5.0192 mL | |
| 10 mM | 0.2510 mL | 1.2548 mL | 2.5096 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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