In vitro, Grapiprant inhibits [(3)H]PGE(2) binding to both human and rat EP(4) receptors with K(i) of 13 +/- 4 and 20 +/- 1 nM, respectively. Grapiprant is highly selective for the human EP(4) receptor over other human prostanoid receptor subtypes. Grapiprant also inhibits PGE(2)-evoked elevation in intracellular cAMP at the human and rat EP(4) receptors with pA(2) of 8.3 +/- 0.03 and 8.2 +/- 0.2 nM, respectively.
In vivo, oral administration of Grapiprant significantly reduces thermal hyperalgesia induced by intraplantar injection of PGE(2) (ED(50) = 12.8 mg/kg).
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||DMSO 10 mM|
Detection and quantification of the selective EP4 receptor antagonist CJ-023423 (grapiprant) in canine plasma by HPLC with spectrofluorimetric detection.
Vito V, et al. J Pharm Biomed Anal. 2016 Jan 25;118:251-258. PMID: 26580822.
Evaluation of the safety of long-term, daily oral administration of grapiprant, a novel drug for treatment of osteoarthritic pain and inflammation, in healthy dogs.
Rausch-Derra LC, et al. Am J Vet Res. 2015 Oct;76(10):853-9. PMID: 26413822.
Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis.
Okumura T, et al. J Pharm Pharmacol. 2008 Jun;60(6):723-30. PMID: 18498708.
|Related Prostaglandin Receptor Products|
Omidenepag,a pharmacologically active form of Omidenepag Isopropyl, is a selective, non-prostanoid EP2 receptor agonist, with an EC50 of 1.1 nM.
Ralinepag (APD811) is a potent, orally bioavailable and non-prostanoid prostacyclin (IP) receptor agonist with EC50 of 8.5 nM, 530 nM and 850 nM for human IP receptor, rat IP receptor and human DP1 receptor, respectively.
GW627368X is a novel, potent and selective competitive antagonist of prostanoid EP4 receptors with additional human TP receptor affinity.
Taprenepag, also known as CP-544326, is a potent and selective EP(2) receptor agonist, with IC50 values of 10 and 15 nM for human and rat EP2, respectively.
Darbufelone is a dual inhibitor of cellular PGF2α and LTB4 production, it is also a COX-2 inhibitor potentially for the treatment of rheumatoid arthritis.
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