Emavusertib (CA-4948) hydrochloride, a selective and potent IRAK4/FLT3 inhibitor, is designed for oral administration. It achieves an IC 50 of 57 nM against IRAK4 in a FRET kinase assay and demonstrates anti-tumor activity [1] [2] [3].

IRAK4:57 nM

Emavusertib exhibits over 350 times greater binding affinity for IRAK-4 compared to IRAK 1, 2, and 3 [3]. At a concentration of 10 μM over 72 hours, Emavusertib reduces the percentage of proliferating cells in marginal zone lymphoma (MZL) cell lines and moderately increases the sub-G0 fraction [3]. It also significantly induces apoptosis in MZL cells, particularly when combined with Ibrutinib [3].

Emavusertib administered orally at doses ranging from 25-150 mg/kg once daily for a consecutive period of 14 days was found to effectively inhibit tumor growth in mice [3]. The animal model used involved mice harboring OCI-LY10 tumors [3]. Dosages were administered either once daily at 25, 50, or 150 mg/kg, or twice daily at 12.5, 25, or 50 mg/kg. The results demonstrated that the fractional dosing of Emavusertib twice daily showed equivalent anti-tumor activity to the corresponding once-daily dosages, such as 12.5 mg/kg (twice daily) versus 25 mg/kg (once daily).