Description
Asciminib is the first-in-class Specifically Targeting the ABL1 Myristoyl Pocket (STAMP) inhibitor, which was granted accelerated approval in 2021 for patients with Philadelphia chromosomepositive (Ph+) chronic myeloid leukemia (CML) in chronic phase, previously treated with two or more tyrosine kinase inhibitors (TKIs), and for adult patients with Ph+ CML in chronic phase with the T315I mutation. Asciminib binds to a myristoyl site of the BCR-ABL1 protein and locks the protein into an inactive conformation through a mechanism distinct from those of all other orthosteric TKIs such as imatinib, thus overcoming drug resistance arising from ATPbinding site mutations. Asciminib mimics the function of the myristoylated N-terminus of ABL1 and restores the natural autoinhibition of the ABL1b protein.
