H118

H118 is a small molecule dual inhibitor of FMS-like tyrosine kinase 3 (FLT3) and MAP kinase-interacting kinases (MNK1/2). Developed by researchers at Shenyang Pharmaceutical University and the Icahn School of Medicine at Mount Sinai, H118 was optimized from a pyrido[3,2-d]pyrimidine scaffold to selectively target FLT3-ITD and MNK while reducing activity against PIM kinases. It is specifically designed to overcome resistance to FLT3 inhibitors like sorafenib in acute myeloid leukemia (AML). By inhibiting both FLT3 and the MNK/eIF4E signaling axis, H118 reduces the expression of downstream oncogenic proteins such as c-Myc and Mcl-1, demonstrating potent antiproliferative activity in sorafenib-resistant FLT3-ITD AML cell lines.