| Description |
Vidupiprant (AMG 853) is a phenylacetic acid derivative. Vidupiprant is a potent and orally active CRTH2 (DP2) and prostanoid D receptor (DP or DP1) dual antagonist with IC50s of 3 nM and 4 nM in buffer, and 8 nM and 35 nM in human plasma, respectively. Vidupiprant has the potential for asthma treatment[1].
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| Related Catalog |
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| Target |
Prostaglandin Receptor[1]
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| In Vitro |
Vidupiprant (AMG 853, Compound 2) inhibits the prostaglandin D2 (PGD2)-induced down-modulation of CRTH2 on CD16 negative granulocytes (eosinophils) in human whole blood with a Kb of 0.2 nM. Vidupiprant also inhibits PGD2-induced cAMP response in platelets in 80% human whole blood with a Kb of 4.7 nM, which is significantly improved, as compared to the Kb of 148 nM of AMG 009. In addition, Vidupiprant demonstrates similar antagonist activity in an aequorin assay using CRTH2-transfected HEK 293 cells and an eosinophil shape change assay, as compared to the CRTH2 receptor down-modulation human whole blood assay[1].
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| In Vivo |
The significant improvement of DP potency of Vidupiprant (AMG 853, Compound 2) over AMG 009 is also demonstrated in vivo in a guinea pig model of PGD2-induced airway constriction. In this model, airway resistance is measured in response to PGD2 challenge. The in vitro guinea pig DP potency is evaluated in guinea pig whole blood cAMP assay.Vidupiprant has a Kb of 5 nM, while the Kb of AMG 009 is 82 nM[1].
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| References |
[1]. Liu J, et al. Discovery of AMG 853, a CRTH2 and DP Dual Antagonist. ACS Med Chem Lett. 2011 Mar 2;2(5):326-30.
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