MEK/RAF molecular glue IK-595

An orally bioavailable mitogen-activated protein kinase kinase (MAP2K, MAPK/ERK kinase, or MEK)/RAF molecular glue and dual kinase inhibitor, with potential antineoplastic activity. Upon oral administration, MEK/RAF molecular glue IK-595 targets and glues B-RAF and C-RAF protein kinases with MEK, forming stable and inactive MEK-RAF complexes. This prevents RAF-dependent phosphorylation and activation of MEK, inhibits the activity of MEK, thereby preventing the activation of MEK-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. In addition, this inhibits the anti-apoptotic activity of C-RAF, which may also inhibit tumor cell proliferation. Oncogenic mutations in RAF plays a key role in the overactivation of the RAS-mitogen-activated protein kinase (MAPK) pathway and drives tumor cell proliferation and survival. MEK1/2 are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway that regulates cell growth. This pathway is often dysregulated in a variety of tumor cell types. CRAF-mediated reactivation of MEK and MAPK signaling leads to resistance to MEK inhibitors. IK-595 is able to cross the blood-brain barrier (BBB).