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  4. KW-5805

KW-5805 is an orally effective anti-ulcer agent that potently inhibits gastric injury induced by various necrotizing agents. KW-5805 enhances the activity of gastric mucosal glucosamine synthetase, increases the levels of gastric adherent mucus and mucosal glycoproteins, and promotes the biosynthesis, storage and secretion of gastric mucus. KW-5805 inhibits the reduction of gastric mucosal blood volume and oxygen supply caused by hemorrhagic shock. KW-5805 suppresses the development of experimental gastric and duodenal ulcers, necrotizing agent-induced gastric mucosal injury, and induced gastric acid secretion. KW-5805 can be used in ulcer-related research.

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KW-5805

KW-5805 Chemical Structure

CAS No. : 113302-01-5

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Description

KW-5805 is an orally effective anti-ulcer agent that potently inhibits gastric injury induced by various necrotizing agents. KW-5805 enhances the activity of gastric mucosal glucosamine synthetase, increases the levels of gastric adherent mucus and mucosal glycoproteins, and promotes the biosynthesis, storage and secretion of gastric mucus. KW-5805 inhibits the reduction of gastric mucosal blood volume and oxygen supply caused by hemorrhagic shock. KW-5805 suppresses the development of experimental gastric and duodenal ulcers, necrotizing agent-induced gastric mucosal injury, and induced gastric acid secretion. KW-5805 can be used in ulcer-related research[1][2].

In Vivo

KW-5805 (30 mg/kg; p.o.) significantly increases the amount of mucus adhering to gastric mucosa, the hexose content of mucosal glycoproteins, and the activity of glucosamine synthetase in male Donryu rats[1].
KW-5805 (10-30 mg/kg; p.o.) significantly maintains gastric mucosal blood volume and oxygen supply adequacy during hemorrhagic shock, while the 30 mg/kg oral dose significantly alleviates ischemia-reperfusion-induced gastric mucosal vascular injury in male Donryu rats[1].
KW-5805 (p.o.) potently inhibits water immersion stress-induced gastric ulcers in male Donryu rats with an ED50 of 3.5 mg/kg; potently inhibits aspirin-induced gastric ulcers with an ED50 of 1.2 mg/kg; potently inhibits indomethacin-induced gastric ulcers with an ED50 of 10.0 mg/kg; potently inhibits mepirizole-induced duodenal ulcers with an ED50 of 6.8 mg/kg; potently inhibits 0.6 N HCl-induced gastric mucosal lesions with an oral ED50 of 39.8 mg/kg; and potently inhibits acidified taurocholate-induced gastric mucosal lesions with an oral ED50 of 11.8 mg/kg[2].
KW-5805 (4.5-10 mg/kg; p.o., s.c.) potently inhibits gastric mucosal injury induced by 99.5% ethanol in male Donryu rats, with an oral ED50 of 4.5 mg/kg, and oral or subcutaneous administration at a dose of 10 mg/kg significantly alleviates the injury[2].
KW-5805 (3-30 mg/kg; intradermal injection) slightly inhibits gastric acid secretion in pylorus-ligated male Donryu rats, and at the dose of 30 mg/kg i.d., it significantly reduces gastric juice volume and acid output by 30%[2].
KW-5805 (10-30 mg/kg; intravenous administration) significantly inhibits acetylcholine- and tetragastrin-stimulated gastric acid secretion in male Donryu rats with acute gastric fistula2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Donryu (male, 190-210 g)[1]
Dosage: 30 mg/kg
Administration: p.o.
Result: Raised gastric adherent mucus volume relative to saline.
Elevated mucosal glycoprotein hexose content versus saline.
Boosted gastric mucosal glucosamine synthetase activity compared with saline.
Animal Model: Donryu (male, 190-210 g, hemorrhagic shock-induced gastric mucosal injury model)[1]
Dosage: 10-30 mg/kg
Administration: p.o.; 1 hour before induction of hemorrhagic shock
Result: Attenuated hemorrhagic shock-induced reductions in gastric mucosal blood volume and oxygen availability at all time points.
Inhibited ischemia-reperfusion-mediated Evans blue extravasation in gastric mucosa at 30 mg/kg.
Animal Model: Donryu rats (male, 190-210 g, 99.5% ethanol-induced gastric mucosal lesions model, 36-hour fasted)[2]
Dosage: 10 mg/kg (p.o.); 10 mg/kg (s.c.)
Administration: p.o.; single dose (30 minutes before ethanol); s.c.; single dose (30 minutes before ethanol)
Result: Lowered lesion index to 12 mm (10 mg/kg p.o.) and 10 mm (10 mg/kg s.c.).
Possessed superior cytoprotective potency versus pirenzepine and cimetidine.
Animal Model: Donryu rats (male, 190-210 g, pylorus-ligated gastric hypersecretion model, 48-hour fasted)[2]
Dosage: 3 mg/kg; 10 mg/kg; 30 mg/kg
Administration: i.d.; single dose (immediate post-ligation)
Result: Cut gastric volume to 2.8 mL with 30% suppression at 30 mg/kg i.d.
Lowered total acid output to 82.0 μEq/hr with 30% suppression at 30 mg/kg i.d.
Displayed weaker antisecretory activity, 3-10-fold less potent than pirenzepine and cimetidine.
Animal Model: Donryu rats (male, 190-210 g, acute gastric fistula gastric hypersecretion model, 24-hour fasted)[2]
Dosage: 10 mg/kg; 30 mg/kg
Administration: i.v.; single dose (30 minutes before secretagogue)
Result: Suppressed methacholine-stimulated gastric acid secretion at 10 and 30 mg/kg i.v.
Exhibited equivalent inhibition to 1 mg/kg i.p. pirenzepine against methacholine-induced acid output at 30 mg/kg i.v.
Inhibited tetragastrin-evoked gastric acid secretion at 30 mg/kg i.v.
Molecular Weight

420.80

Formula

C19H28Cl3N3O
CAS No.
SMILES

CCN(CC)CCNC1C2=CC=CC=C2OCC3=NC=CC=C31.[H]Cl.[H]Cl.[H]Cl
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Keywords:

KW-5805113302-01-5KW5805KW 5805Biochemical Assay Reagentsgastric acid secretionglucosamine synthetasemale Donryu ratsgastric mucustetragastrinhemorrhagic shockgastric ulcerduodenal ulcerischemia-reperfusionmucosal glycoproteinInhibitorinhibitorinhibit

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