Emavusertib

Emavusertib is an orally active inhibitor for IRAK4 (IC₅₀=57 nM) and FLT3. Emavusertib inhibits NF-κB and MyD88 signaling pathways, reduces the generation of pro-inflammatory cytokines like IL-6 and IL-10, thereby exhibiting anti-inflammatory and anti-proliferative activities against cancer cells, leading to cell apoptosis. Emavusertib exhibits antitumor activity in mouse model In Vitro:Emavusertib (CA-4948) is over 500-fold more selective for IRAK-4 compared to IRAK-1. Emavusertib reduces TNF-α, IL-1β, IL-6 and IL-8 release from TLR-Stimulated THP-1 Cells with an IC₅₀ <250 nM. Emavusertib also has antiproliferative activity due to inhibition of receptor-type tyrosine-protein kinase FLT3^[1].
Emavusertib exhibits >350-fold higher binding affinity for IRAK-4 than that observed for IRAKs 1, 2 and 3^[3].
Emavusertib (10 μM, 72 h) decreases the percentage of proliferating cells and induces a moderate increase in the sub-G0 fraction in marginal zone lymphomas (MZL) cell lines^[3].
Emavusertib (10 μM, 72 h) induces a significant increase in the apoptotic cell population of MZL cells, particularly when combined with Ibrutinib (HY-10997) compared to ibrutinib and emavusertib alone^[3].
In Vivo:Emavusertib (CA-4948) shows anti-tumor activity in animal models including tumors containing MyD88 gene mutations. Emavusertib shows antileukemic activity in mouse models of FLT3 wild-type and FLT3 mutated acute myeloid leukemia (AML)^[1].
Emavusertib (25-150 mg/kg, Orally, once daily, for 14 consecutive days) induces tumor growth inhibition in mice^[3].