L-365260 is an orally bioactive and selective non-peptide gastrin and brain cholecystokinin receptor (CCK-B) antagonist (inhibitor) with Kis values of 1.9 nM and 2.0 nM, respectively. L-365260 interacts with guinea pig gastrin and brain CCK receptors in a stereoselective and competitive manner. L-365260 enhances the pain-relief activity of Morphine and prevents Morphine tolerance.

Physicochemical Properties

Molecular Formula	C24H22N4O2
Molecular Weight	398.47
Exact Mass	398.174
CAS #	118101-09-0
Related CAS #	L-365260 hemihydrate
PubChem CID	5311201
Appearance	White to off-white solid powder
Density	1.23g/cm3
Boiling Point	611.5ºC at 760 mmHg
Flash Point	323.6ºC
Vapour Pressure	6.85E-15mmHg at 25°C
Index of Refraction	1.648
LogP	3.921
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	30
Complexity	658
Defined Atom Stereocenter Count	1
SMILES	CC1=CC(=CC=C1)NC(=O)N[C@H]2C(=O)N(C3=CC=CC=C3C(=N2)C4=CC=CC=C4)C
InChi Key	KDFQABSFVYLGPM-QFIPXVFZSA-N
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
Chemical Name	1-[(3R)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea
Synonyms	L365260; L 365260; L-365260
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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].
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.
References	[1]. A new potent and selective non-peptide gastrin antagonist and brain cholecystokinin receptor (CCK-B) ligand: L-365,260. Eur J Pharmacol. 1989 Mar 21;162(2):273-80. [2]. Cholecystokinin action on layer 6b neurons in somatosensory cortex. Brain Res. 2009 Jul 28;1282:10-9. [3]. The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat. Eur J Pharmacol. 1990 Jan 25;176(1):35-44.
Additional Infomation	L-365260 is a benzodiazepine.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~250.97 mM)

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.