APH02174 is a highly selective and orally active IRAK4PROTAC degrader, with a DC50 of 4.01 nM in THP-1 cells. It blocks inflammatory signaling by inhibiting IL-6 release and is applicable for researching inflammatory diseases such as psoriasis and rheumatoid arthritis.

IRAK4:4.01 nM (DC50)

APH02174, in the concentration range of 0.24-1000 nM, selectively degrades IRAK4 protein in various cells, including THP-1 (DC50 = 4.01 nM), hPBMCs (DC50 = 0.43 nM), and mouse PBMCs (DC50 = 3.57 nM). Additionally, at 0.03-2000 nM for 24 hours, APH02174 significantly inhibits LPS-induced IL-6 release in hPBMCs with an IC50 of 16.43 nM.

APH02174 administered orally at doses of 10-100 mg/kg twice daily for 7 days can reduce skin inflammation induced by IMQ and degrade IRAK4 protein levels in the spleen of psoriatic mice. Additionally, APH02174 at 30 or 100 mg/kg once daily for 14 days significantly alleviates arthritis in rheumatoid arthritis mouse models.