KME-4
KME-4 is an orally active dual inhibitor of 5-lipoxygenase (5-lipoxygenase) and cyclooxygenase (cyclooxygenase). KME-4 inhibits 5-lipoxygenase in the cytosol of guinea pig polymorphonuclear leukocytes (PMNL) and cyclooxygenase in rabbit platelets, with IC50 values of 0.85 μM and 0.44 μM, respectively. KME-4 can be used in studies related to arachidonic acid metabolism, inflammatory responses, and arthritis.
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- CAS No.: 83677-24-1
- Formule: C19H26O3
- Masse moléculaire:302.41
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
Description
In Vitro
KME-4 inhibits prostaglandin synthase activity in lyophilized bovine seminal vesicle microsomes, with an IC50 of 22.5 μM[5].
KME-4 inhibits prostaglandin synthase activity in the supernatant of rat basophilic leukemia (RBL-1) cells, with an IC50 of 0.74 μM[5].
KME-4 inhibits 5-lipoxygenase activity in the supernatant of rat basophilic leukemia (RBL-1) cells, with an IC50 of 1.3 μM[5].
KME-4 (0.05-400 μM; 1 min preincubation) completely inhibits platelet aggregation in rabbit platelet-rich plasma induced by Arachidonic acid (HY-109590) at a concentration of 0.2 μM, but exerts no effect on aggregation induced by ADP (HY-W010918) even at concentrations up to 400 μM[5].
KME-4 potently inhibits 5-lipoxygenase activity in the cytosolic fraction of guinea pig peritoneal polymorphonuclear leukocytes, with an IC50 of 0.85 μM[2].
KME-4 inhibits 5-lipoxygenase activity in intact guinea pig peritoneal polymorphonuclear leukocytes stimulated with the ionophore A23187 (HY-N6687), with an IC50 of 11.5 μM[2].
KME-4 potently inhibits cyclooxygenase activity in ultrasonically disrupted rabbit platelets, with an IC50 of 0.44 μM, but does not inhibit platelet 12-lipoxygenase activity even at concentrations as high as 100 μM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
KME-4 (3-30 mg/kg; p.o.; single administration) exhibits dose-dependent analgesic activity in the yeast-induced paw edema Randall-Selitto assay in rats, and significantly increases the paw pressure threshold of the inflamed paw at an oral dose of 30 mg/kg [4].
KME-4 (3-30 mg/kg; p.o.; single administration) exhibits only weak analgesic activity in the rat adjuvant-induced arthritis pain model at oral doses up to 30 mg/kg[4].
KME-4 (10 mg/kg/day; p.o.; once daily; 28 days) reduces paw swelling, promotes body weight gain, restores the weights of the thymus, spleen, adrenal glands and iliac lymph nodes, and decreases ESR from 9.54 mm/h in the adjuvant control group to 1.94 mm/h in the rat adjuvant arthritis model; at 1 mg/kg/day, it also reduces paw swelling and decreases ESR to 4.14 mm/h[4].
KME-4 (2-10 mg/kg/day; p.o.; administered once daily for 7 consecutive days) inhibits filter paper-induced granuloma formation in male Wistar rats, with an ED25 of 2.2 mg/kg/day[5].
KME-4 (0.5-50 mg/kg; p.o.; single administration) reduces yeast-induced pyrexia in male Wistar rats at doses of 0.5-10 mg/kg (p.o.), and does not alter normal body temperature at doses up to 50 mg/kg[5].
KME-4 (1-10 mg/kg; p.o.; single administration) completely prevents arachidonic acid-induced acute death in male Japanese white rabbits at a dose of 10 mg/kg (p.o.)[5].
KME-4 (2-10 mg/kg; p.o.; once daily; for 14 consecutive days) ameliorates the systemic symptoms of established adjuvant-induced arthritis in rats in a dose-dependent manner, including reducing paw swelling, restoring body weight gain, normalizing organ weights, ESR and serum A/G ratio, and attenuating bone damage; no rebound swelling is observed at doses of 5 and 10 mg/kg, and no severe disease signs appear at all at the 10 mg/kg dose [3].
KME-4 (1-10 mg/kg; p.o.; 1 h before Carrageenan (HY-125474)) reduces pleural exudate volume and total leukocyte count in the 5 h Carrageenan-induced pleurisy model in rats, where approximately 95% of the leukocytes at this stage are neutrophils[1].
KME-4 (3-30 mg/kg; p.o.; 1 h before Carrageenan) dose-dependently reduces the total number of neutrophils and monocytes in 24-hour pleurisy, preferentially decreasing the monocyte count by approximately 60%, while not significantly altering the exudate volume at the tested doses[1].
KME-4 (10 or 30 mg/kg; p.o.; administered 5 h after Carrageenan) reduces the total leukocyte count, monocyte count, and exudate volume in 24-h pleurisy even when dosed after the inflammatory response has already occurred, while exerting a minor effect on neutrophil count[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Wistar rats (male, 130-150 g)[4]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose; 30 min before Acetic acid
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Result:Reduced dye leakage by 63.7% at 3 mg/kg.
Reduced dye leakage by 55.4% at 10 mg/kg.
Reduced dye leakage by 79.0% at 30 mg/kg.
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Animal Model:Wistar rats (male, ~200 g)[4]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose
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Result:Showed analgesic activity in adjuvant arthritic rats, with a weaker effect than reference drugs at tested doses.
Produced a reduction in squeak count over 5 hours after administration at 30 mg/kg.
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Animal Model:Wistar rats (male, 250-290 g, adjuvant-induced arthritis)[4]
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Dosage:1 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 28 days
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Result:Reduced paw swelling at 1 and 10 mg/kg/day.
At 10 mg/kg/day, promoted body-weight gain and recovered thymus, spleen, adrenal and iliac lymph-node weights.
Reduced ESR from 9.54 mm/h in adjuvant controls to 4.14 mm/h at 1 mg/kg/day and 1.94 mm/h at 10 mg/kg/day.
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Animal Model:Wistar (male, 150-200 g, paper disk-induced granuloma formation model)[5]
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Dosage:2 mg/kg/day; 5 mg/kg/day; 10 mg/kg/day
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Administration:p.o.; daily; 7 days
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Result:Showed dose-dependent inhibition of granuloma formation: produced 25% inhibition at 2 mg/kg/day, 31% inhibition at 5 mg/kg/day, and 40% inhibition at 10 mg/kg/day.
Achieved an ED25 (dose producing 25% inhibition of granuloma formation) of 2.2 mg/kg/day.
Did not reduce body weight gain or increase adrenal weights at tested doses.
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Animal Model:Wistar (male, 180-200 g, yeast-induced fever model)[5]
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Dosage:0.5 mg/kg; 2 mg/kg; 10 mg/kg; 50 mg/kg
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Administration:p.o.; single dose
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Result:Produced a significant reduction in yeast-induced fever at doses of 0.5-10 mg/kg.
Did not affect the body temperature of normal rats at doses up to 50 mg/kg.
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Animal Model:Japanese White (male, 2.5-3.5 kg, arachidonic acid-induced acute death model)[5]
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Dosage:1 mg/kg; 5 mg/kg; 10 mg/kg
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Administration:p.o.; single dose
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Result:Prevented arachidonic acid-induced death in rabbits: mortality was 3/5 at 1 mg/kg, 1/5 at 5 mg/kg, and 0/5 at 10 mg/kg.
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Animal Model:Wistar rats (male, 10 weeks old, intrapleural λ-carrageenan-induced inflammation)[1]
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Dosage:1 mg/kg (1h pre-carrageenan); 3 mg/kg (1h pre-carrageenan); 10 mg/kg (1h pre-carrageenan); 30 mg/kg (1h pre-carrageenan); 10 mg/kg (5h post-carrageenan); 30 mg/kg (5h post-carrageenan)
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Administration:p.o.; 1 hour before carrageenan injection; p.o.; 5 hours after carrageenan injection
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Result:Reduced exudate volume and total cell counts at 1 mg/kg when administered 1 hour before carrageenan for 5-hour pleurisy.
Reduced exudate volume by ~40% and total cell counts by ~25% at 3 mg/kg when administered 1 hour before carrageenan for 5-hour pleurisy.
Reduced exudate volume by ~40% and total cell counts by ~25% at 10 mg/kg when administered 1 hour before carrageenan for 5-hour pleurisy.
Reduced total cell numbers and monocyte numbers at 3 mg/kg when administered 1 hour before carrageenan for 24-hour pleurisy.
Reduced total cell numbers, neutrophil numbers, and monocyte numbers by ~45% at 10 mg/kg when administered 1 hour before carrageenan for 24-hour pleurisy.
Reduced total cell numbers, neutrophil numbers, and monocyte numbers by ~60% at 30 mg/kg when administered 1 hour before carrageenan for 24-hour pleurisy, with no significant effect on exudate volume at any dose.
Reduced exudate volume, total cell numbers, and monocyte numbers at 10 mg/kg when administered 5 hours after carrageenan for 24-hour pleurisy.
Reduced exudate volume by ~30%, total cell numbers, and monocyte numbers by ~20% at 30 mg/kg when administered 5 hours after carrageenan for 24-hour pleurisy, with little effect on neutrophil numbers.
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Animal Model:Wistar Lewis (male, 220-260 g, adjuvant-induced rheumatoid arthritis model)[3]
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Dosage:2 mg/kg; 5 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 14 days (day 14-27)
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Result:Dose-dependently suppressed swelling of both injected and uninjected hindpaws.
Promoted recovery of body-weight gain.
Maintained suppression of paw swelling for approximately 2 weeks after dosing stopped at 5 and 10 mg/kg.
Reversed abnormalities in thymus, spleen and adrenal weights.
Restored elevated ESR and decreased serum A/G ratio toward normal values.
Restored ESR to near-normal levels at 5 and 10 mg/kg.
Reduced radiographic bone-damage scores at 5 and 10 mg/kg.
No severe disease signs were observed in 0/6 rats at 10 mg/kg.
Chemical Information
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CAS No. 83677-24-1
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Masse moléculaire 302.41
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Formule C19H26O3
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SMILES
O=C1OCCC1=CC=2C=C(C(O)=C(C2)C(C)(C)C)C(C)(C)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KME-4 Related Classifications
HY-19014 Related Classifications
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