L 888607

L 888607 is a potent, and selective CRTH2 (also known as DP2) agonist with a Ki of 0.8±0.4 nM.

Signaling Pathways >> GPCR/G Protein >> Prostaglandin Receptor

Research Areas >> Inflammation/Immunology

CRTH2/DP2 Receptor:0.8 nM (Ki)

DP/DP1 Receptor:2331 nM (Ki)

TP Receptor:283 nM (Ki)

EP2 Receptor:8748 nM (Ki)

EP3-III Receptor:1260 nM (Ki)

EP4 Receptor:4634 nM (Ki)

FP Receptor:10018 nM (Ki)

IP Receptor:14434 nM (Ki)

L 888607 (L-888,607) is administered to mice either intravenously (i.v.) or orally (p.o.) to determine its pharmacokinetic profile over an 8-h period. After an intravenous administration of 5 mg/kg L 888607, blood analysis reveals a peak level (Cmax) of 36.1 μM, a half-life (t1/2) of 2.9 h, a trough level at 8 h (C8h) of 3.5 μM, and an area under the curve0-8h of 87.1 μM. After oral administration of 20 mg/kg L 888607, blood analysis reveals a Cmax of 31.6 μM, a t1/2 of 4 h, a C8h at 8 h of 15.4 μM, an area under the curve0-8h of 166 μM, and a bioavailability of 48%[1].

Mice[1] Male (ICR)BR mice with an average weight of 42 g are used. A single dose [5 mg/kg in 60% (v/v) polyethylene glycol 200] of L 888607 is given intravenously via the saphenous vein or a single dose (20 mg/kg in 60% (v/v) polyethylene glycol 400) is given orally by gavage. No obvious side effects are observed. Blood (10 μL) is taken from the jugular vein at each time point indicated and added to 30 μL of 0.1 M aqueous trisodium citrate. The mixture is kept at -20°C until analysis[1].

[1]. Gervais FG, Identification of a potent and selective synthetic agonist at the CRTH2 receptor. Mol Pharmacol. 2005 Jun;67(6):1834-9.

[2]. Ulven T, et al. Novel CRTH2 antagonists: a review of patents from 2006 to 2009. Expert Opin Ther Pat. 2010 Nov;20(11):1505-30.

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