CAY10471 is a Selective and Orally Active CRTH2 Antagonist

CAY10471 (TM30089) is a potent, selective, and orally active prostaglandin D2 receptor CRTH2 antagonist. In PC12 cells, CAY10471 blocks 15d-PGJ2-induced p38 MAP kinase activation and decreases phosphorylation of p-38 MAP kinase.

Prostaglandin D2 (PGD2) is a prostanoid that always collects to allergic inflammation. PGD2 plays its role through the CRTH2 and DP receptors. 5% 2,4,6-trinitrochlorobenzene (TNCB) can induce chronic contact hypersensitivity (CHS). DP-/- mice and CRTH2-/-/DP-/- mice show exacerbated chronic CHS. However, CRTH2-/- mice exert diminished-responses.

Skin responses always exhibit local versions of IL-13, CCL11, and CCL22. Besides, Chronic CHS and acute CHS are mediated by Th2 and Th1/Th17 immunity, respectively. Oral administration of CAY10471 attenuates and decreases inflammation in the CHS model.

Lipocalin-type PGD2 synthase (L-PGDS) is a secretory protein of the lipocalin superfamily. It can convert the precursor of prostanoids PGH2 to PGD2. Under conditions of tubulointerstitial stress, PGD2 interacts with two receptors, one is the prostanoid DP1 receptor and the other is CRTH2. DP1 receptor activation produces vasodilation and bronchodilation. Moreover, the DP1 receptor is going to controls various functions, including cytokine production in dendritic cells.

CRTH2 belongs to the family of chemokine receptors. Through the recruitment of Th2 lymphocytes and other leukocytes, CRTH2 activation plays an important role in allergic inflammation. Furthermore, it can drive the production of the Th2 cytokines IL-4, IL-5, and IL-13.

In C57BL/6 mice, CAY10471 can significantly attenuate interstitial collagen deposition in the cortex. When compares to the vehicle, the percentage decreases to 8.40%. After unilateral ureteral obstruction (UUO), CAY10471 oral administration from 3 days significantly attenuates interstitial collagen deposition in the cortex compared with vehicle (9.63% versus 14.44%). However, oral treatment beginning 5 days after UUO has little effect on interstitial collagen deposition in the cortex.

In conclusion,  as a selective and orally active CRTH2 Antagonist, CAY10471 attenuates the progression of tubulointerstitial fibrosis and chronic contact hypersensitivity (CHS) in the animal models.


Matsushima Y, et al. Mol Immunol. 2011 Oct;49(1-2):304-10.