S 38093

Catalog No.S8598 Batch:S859801

Technical Data

Formula

C₁₇H₂₄N₂O₂

Molecular Weight

288.38

CAS No.

862896-30-8

Solubility (25°C)*

In vitro

DMSO

57 mg/mL (197.65 mM)

Ethanol

57 mg/mL (197.65 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

S 38093 is a histamine H3 antagonist/inverse agonist with a moderate affinity for rat, mouse and human H3 receptors (Ki = 8.8, 1.44 and 1.2 μM, respectively) and no affinity for other histaminergic receptors.

Targets

human H3 receptor ^[1]	mouse H3 receptor ^[1]	rat H3 receptor ^[1]
1.2 μM(Ki)	1.44 μM(Ki)	8.8 μM(Ki)

In vitro

In cellular models, this compound was able to antagonize mice H3 receptors (KB = 0.65 μM) and to suppress cAMP decrease induced by an H3 agonist via human H3 receptors (KB = 0.11 μM). Among the four histaminergic receptor subtypes, it is selective for the H3 receptor, its binding affinity for H1, H2 and H4 receptors being negligible^[1].

In vivo

S 38093, a novel brain-penetrant antagonist/inverse agonist of H3 receptors, on AHN (proliferation, maturation and survival) in 3-month-old and in aged 16-month-old mice. In aged animals, this compound induced a reversal of age-dependent effects on hippocampal brain-derived neurotrophic factor (BDNF) BDNF-IX, BDNF-IV and BDNF-I transcripts and increased vascular endothelial growth factor (VEGF) expression. The effects of chronic administration of this compound were assessed on a neurogenesis-dependent “context discrimination (CS) test” in aged mice. While ageing altered mouse CS, chronic treatment with this chemical significantly improved CS. Chronic treatment with this compound increases adult hippocampal neurogenesis and may provide an innovative strategy to improve age-associated cognitive deficits. This compound is found to be active at a mean pharmacological dose of 0.3–1 mg/kg p.o./i.p. in animal behavioral tests of working memory (Morris water maze in rats; spontaneous alternation and concurrent serial alternation tests in mice; delayed matching to sample in aged monkeys) and episodic-like memory (social and object recognition tests in rats; contextual discrimination task in mice). It also improves attention, executive functioning, and cognitive flexibility in MPTP-treated monkeys. Moreover, in line with its H3 antagonist/inverse agonist properties, this chemical dose-dependently increases extracellular histamine levels in the prefrontal cortex and facilitates cholinergic transmission in the prefrontal cortex and hippocampus of rats after both acute and chronic administrations^[2]. This compound was rapidly absorbed in mouse and rat (Tmax= 0.25-0.5h), slowly in monkey (2h), with a bioavailability ranging from 20 to 60% and t1/2 ranging from 1.5h to 7.4h. The compound was widely distributed with a moderate volume of distribution and low protein binding. The brain distribution of this chemical was rapid and high^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines HEK-293 cells Concentrations 0.01-100 μM Incubation Time 1 h Method The cells (2 x 10⁶ per ml) were harvested and suspended in Hank's balanced salt solutions/HEPES (pH7.4) buffer containing 1 mM isobutyl-methylxanthine and 1mg/ml of BSA. The fluor 647-anti cAMP antibody solution (1 μl) was added to the cell suspension (100 μl) and 6 μl aliquots of this mix were dispensed in white 384-well microtiter plates. The cells were then incubated with 6 μl aliquots of S 38093 and/or the reference compounds (specific H3 agonist Imetit or antagonist Thioperamide) at increasing concentrations (0.01-100 μM), in the presence of forskolin (FSK, 0.5 μM final concentration) in order to preactivate adenylate cyclase. After a 1 h incubation at room temperature in the dark, the lysis buffer (0.35% Triton X-100, 10mM CaCl2, 50mM HEPES) containing LANCE EU-W8044 labeled streptavidin and biotinyled cAMP was added to the cells. After a 20 h incubation at + 4°C in the dark, plates were read on an microplate reader.
Animal Study:^{^[2]}	Animal Models C57Bl/6JRj male mice Dosages 0.3, 1 and 3 mg/kg/day Administration p.o

Cell Assay:^{^[1]}

Cell lines
HEK-293 cells
Concentrations
0.01-100 μM
Incubation Time
1 h
Method
The cells (2 x 10⁶ per ml) were harvested and suspended in Hank's balanced salt solutions/HEPES (pH7.4) buffer containing 1 mM isobutyl-methylxanthine and 1mg/ml of BSA. The fluor 647-anti cAMP antibody solution (1 μl) was added to the cell suspension (100 μl) and 6 μl aliquots of this mix were dispensed in white 384-well microtiter plates. The cells were then incubated with 6 μl aliquots of S 38093 and/or the reference compounds (specific H3 agonist Imetit or antagonist Thioperamide) at increasing concentrations (0.01-100 μM), in the presence of forskolin (FSK, 0.5 μM final concentration) in order to preactivate adenylate cyclase. After a 1 h incubation at room temperature in the dark, the lysis buffer (0.35% Triton X-100, 10mM CaCl2, 50mM HEPES) containing LANCE EU-W8044 labeled streptavidin and biotinyled cAMP was added to the cells. After a 20 h incubation at + 4°C in the dark, plates were read on an microplate reader.

Animal Study:^{^[2]}

Animal Models
C57Bl/6JRj male mice
Dosages
0.3, 1 and 3 mg/kg/day
Administration
p.o

References

https://pubmed.ncbi.nlm.nih.gov/28336400/
https://pubmed.ncbi.nlm.nih.gov/28218311/

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SHIPPING AND STORAGE
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