H104

H104 is a small molecule dual inhibitor of FMS-like tyrosine kinase 3 (FLT3) and MAP kinase-interacting serine/threonine-protein kinase (MNK), specifically developed to treat acute myeloid leukemia (AML) harboring FLT3-ITD mutations. Developed by researchers at Shenyang Pharmaceutical University and the Icahn School of Medicine at Mount Sinai, H104 was optimized from a pyrido[3,2-d]pyrimidine scaffold to selectively target MNK1/2 and FLT3 while minimizing PIM kinase inhibition. The compound is designed to overcome resistance to FLT3 inhibitors like sorafenib, which often arises through overactivation of the mTOR/MNK signaling pathway. By inhibiting both FLT3 and MNK, H104 effectively reduces the phosphorylation of eIF4E and the expression of downstream oncogenic proteins such as c-myc and Mcl-1, leading to potent antiproliferative effects in sorafenib-resistant AML cells.