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^{[1][2][3][4][5]}. 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]. In Vivo:KME-4 (3-30 mg/kg; p.o.; single administration) dose-dependently inhibits vascular permeability induced by Acetic acid (HY-Y0319) in rats, with a maximum inhibition rate of up to 79.0% at the oral dose of 30 mg/kg^[4].
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].