PF-07054894 is an orally active and potent C-C Chemoattractant Cytokine (Chemokine) Receptor 6 (CCR6) antagonist that blocks CCR6-mediated chemotaxis with an IC50 value of 5.7 nM in vitro. PF-07054894 targets G protein-coupled receptor (GPCR). PF-07054894 can be used in research of inflammatory bowel disease.
PF-07054894 (1-3000 nM, 1 h) inhibits CCL20/CCR6-mediated T Cell chemotaxis in an insurmountable manner[2].
PF-07054894 (10 mg/kg, p.o., twice a day for 6 consecutive days) increases circulating CCR6+ T cells in naïve cynomolgus monkeys[2][3].PF-07054894 (100 mg/kg, p.o., once or twice per day for 12 days) is efficacious in interleukin-23-induced inflammation in skin inflammation mouse model[2].
References:
[1]. Gómez S, et, al. Desarrollo de anticuerpos terapéuticos contra el receptor CCR6 humano. [2]. Li W, et al. A Novel C-C Chemoattractant Cytokine (Chemokine) Receptor 6 (CCR6) Antagonist (PF-07054894) Distinguishes between Homologous Chemokine Receptors, Increases Basal Circulating CCR6+ T Cells, and Ameliorates Interleukin-23-Induced Skin Inflammation. J Pharmacol Exp Ther. 2023 Jul;386(1):80-92.
[3]. Li W, et al. A novel CCR6 antagonist (PF-07054894) that distinguishes between homologous chemokine receptors, increases basal circulating CCR6+ T cells, and ameliorates interleukin-23-induced skin inflammation[J]. Journal of Pharmacology and Experimental Therapeutics, 2023. [4]. Chinigo G M, et al. Early Process Development of PF-07054894, a Squaramide-Based Antagonist of C–C Chemokine Receptor Type 6 (CCR6)[J]. Organic Process Research & Development, 2024.