SCH 563705 is a potent and orally available CXCR2 and CXCR1 antagonist, with IC 50 s of 1.3 nM, 7.3 nM and K i s of 1 and 3 nM, respectively.
In Vitro
SCH 563705 (Compound 16) is a potent and orally available CXCR2 and CXCR1 antagonist, with IC 50 s of 1.3 nM, 7.3 nM and K i s of 1 and 3 nM, respectively. SCH 563705 shows potent inhibition against both Gro-a and IL-8 induced human neutrophil migration (chemotaxis IC 50 = 0.5 nM, against 30 nM of Gro-a; chemotaxis IC 50 = 37 nM, against 3 nM of IL-8). SCH 563705 potently inhibits mouse CXCR2 (IC 50 = 5.2 nM). MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
SCH 563705 has good oral pharmacokinetic profiles in rats, mice, monkeys and dogs . SCH 563705 (50 mg/kg p.o) reduces blood Ly6G + Ly6C + neutrophil frequency and unchanged levels of Ly6GLy6Chi monocytes. SCH563705 (3-30 mg/kg p.o) treatment causes a dosedependent elevation in plasma levels of CXCL1. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal administration
Mice Induction of anti-collagen antibody-induced arthritis. Anti-collagen antibody-induced arthritis (ABIA) is induced in BALB/c mice (n = 8 mice per treatment group) as follows. On day 0, mice are injected intraperitoneally with 4 mg ArthritoMAB Arthritis-inducing Antibody Cocktail. On day 3, mice are boosted intraperitoneally with 50 μg of lipopolysaccharide from Escherichia coli 055:B5 in 200 μL sterile PBS. In all studies, SCH 563705 is administered in a vehicle consisting of 0.4% METHOCEL E15 premium hydroxypropyl methylcellulose (MC) . Clinical scores are determined daily as follows. Each paw is assigned a score of 0-4 based on the following criteria: asymptomatic, 0; slight redness, 1; one or more swollen digits in addition to redness, 2; swelling of entire paw, 3; ankylosing of joints and residing of swelling, 4. The sum of the four paw scores for each mouse (0-16) are plotted against time to calculate the area under the curve (AUC) of disease activity. Paw hickness measurements are made daily using a micrometer caliper over the metatarsals of the paw. The percent change in paw thickness relative to baseline (day 0) measurements is then calculated . aladdin has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
IC50& Target:CXCR2 1 nM (Ki) CXCR1 3 nM (Ki) CXCR2 1.3 nM (IC 50 ) CXCR1 7.3 nM (IC 50 ) Mouse CXCR2 5.2 nM (IC 50 )
