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.
For research use only. We do not sell to patients.
- CAS No.: 83677-24-1
- Formula: C19H26O3
- Molecular Weight:302.41
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
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- References
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Help & FAQs
Biological Activity
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. Further protocols information, click here.
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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Molecular Weight 302.41
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Collagen-Induced Arthritis
Collagen-induced arthritis (CIA) is an autoimmune murine model of rheumatoid arthritis in which immunization with type II collagen (CII) emulsified in an adjuvant induces a T cell- and autoantibody-driven inflammatory arthritis characterized by synovial hyperplasia, immune cell infiltration, and joint destruction. The model typically relies on genetically susceptible mouse strains (e. g. , DBA/1) and reproduces key features of human rheumatoid arthritis, including anti-collagen immune responses and progressive joint inflammation. Disease onset generally occurs within ~3-4 weeks after immunization, depending on antigen/adjuvant combinations and protocol variation. The immunopathology is driven by adaptive immune activation against CII, leading to systemic and local joint inflammation mediated by pro-inflammatory cytokines and effector immune cells, making CIA a standard preclinical platform for evaluating immunomodulatory and anti-arthritic interventions.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KME-4 Related Classifications
HY-19014 Related Classifications
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