Avutometinib and Defactinib

**Semantic type:** Pharmacologic Substance

**Definition:** An orally bioavailable co-packaged formulation composed of avutometinib, an inhibitor of the serine/threonine protein kinases Raf and mitogen-activated protein kinase kinase (MAP2K, MAPK/ERK kinase, or MEK), and defactinib, a focal adhesion kinase (FAK) inhibitor, with antineoplastic and antiangiogenic activities. Upon oral administration of avutometinib and defactinib, avutometinib specifically targets, binds to and inhibits the kinase activities of Raf and MEK, resulting in the inhibition of Raf/MEK-mediated signal transduction pathways. This results in the inhibition of Raf/MEK-dependent tumor cell proliferation and survival. Defactinib targets, binds to and inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including those involving RAS/MEK/extracellular signal-regulated kinase (ERK) and PI3K/Akt, thereby inhibiting tumor cell migration, proliferation, survival, and tumor angiogenesis. The RAS/RAF/MEK/ERK signaling pathway is often dysregulated in human cancers and plays a key role in tumor cell proliferation, differentiation and survival. The tyrosine kinase FAK, a signal transducer for integrins, is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types.

**Synonyms:** - Avmapki Fakzynja - Avmapki Plus Fakzynja - Avutometinib and Defactinib Co-pack - Avutometinib and Defactinib Co-packaged Formulation - Avutometinib/Defactinib