Asciminib

Asciminib (brand name Scemblix) is a first-in-class, oral tyrosine kinase inhibitor (TKI) approved by the FDA (initially in Oct 2021, expanded in 2024) for treating adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML), particularly for those with resistance or intolerance to prior TKIs, or harboring the T315I mutation. It functions via a unique, allosteric mechanism—targeting the ABL myristoyl pocket (STAMP)—which distinguishes it from conventional ATP-competitive inhibitors. Common side effects include fatigue, rash, diarrhea, musculoskeletal pain, and upper respiratory tract infections, along with potential liver enzyme elevations. Key Aspects of Asciminib Mechanism of Action (STAMP Inhibitor): Unlike traditional TKIs that compete with ATP, asciminib binds to the ABL1 myristoyl pocket, locking the BCR-ABL1 fusion protein