Merck-22-6

Merck-22-6 (also known as Merck 22) is a potent, selective, and allosteric dual inhibitor of the serine/threonine kinases **Akt1** and **Akt2**. Developed by **Merck & Co.**, it is a widely used research tool in oncology to study the PI3K/Akt/mTOR signaling pathway, which is frequently hyperactivated in human cancers. Unlike traditional ATP-competitive inhibitors, Merck-22-6 binds to an allosteric site at the interface of the pleckstrin homology (PH) and kinase domains. This binding locks the enzyme in a closed, inactive conformation and prevents its translocation to the plasma membrane, a necessary step for its activation by upstream kinases like PDK1. By inhibiting Akt activation, Merck-22-6 suppresses downstream signaling, leading to cell cycle arrest and the induction of apoptosis in various cancer models, including multiple myeloma and breast cancer. It served as a critical structural lead for the development of clinical-stage Akt inhibitors, most notably **MK-2206**.

Other names

Akt1/2 inhibitor Merck-22-6