lomonitinib

An orally bioavailable inhibitor of FMS-like tyrosine kinase 3 (FLT3; CD135; STK1; FLK2) mutations and interleukin-1 receptor-associated kinase 4 (IRAK4), with potential antineoplastic activity. Upon oral administration, lomonitinib targets, binds to and inhibits the activity of FLT3 mutations, including the FLT3-ITD-F691L gatekeeper mutation, while sparing the wild-type form of FLT3. This inhibits the proliferation of FLT3 mutant-expressing cancer cells. In addition, lomonitinib targets, binds to, and inhibits the kinase activity of IRAK4. This inhibits IRAK4-mediated signaling and may reduce adaptive resistance to FLT3 inhibition as toll-like receptor (TLR) activation plays an important role in resistance to FLT3 inhibition. FLT3, a class III receptor tyrosine kinase (RTK), is overexpressed or mutated in most B-lineage neoplasms and in acute myeloid leukemias. IRAK4, a serine/threonine-protein kinase, plays a key role in both the TLR and IL-1R signaling pathways.