Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1.

@article{Schoepfer2018DiscoveryOA,
  title={Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1.},
  author={Joseph Schoepfer and Wolfgang Jahnke and Giuliano Berellini and Silvia Buonamici and Simona Cotesta and Sandra W. Cowan-Jacob and Stephanie Kay Dodd and Peter Drueckes and Doriano Fabbro and Tobias Gabriel and J. M. Groell and Robert Martin Grotzfeld and Abdulkhaleq Q. A. Hassan and Chryst{\`e}le Henry and Varsha Iyer and Darryl S. Jones and Franco Lombardo and Alice Loo and Paul William Manley and Xavier Francois Andre Pelle and Gabriele Rummel and Bahaa Salem and Markus Warmuth and Andrew A. Wylie and Thomas Zoller and Andreas L Marzinzik and Pascal Furet},
  journal={Journal of medicinal chemistry},
  year={2018},
  volume={61 18},
  pages={
          8120-8135
        }
}
Chronic myelogenous leukemia (CML) arises from the constitutive activity of the BCR-ABL1 oncoprotein. Tyrosine kinase inhibitors (TKIs) that target the ATP-binding site have transformed CML into a chronic manageable disease. However, some patients develop drug resistance due to ATP-site mutations impeding drug binding. We describe the discovery of asciminib (ABL001), the first allosteric BCR-ABL1 inhibitor to reach the clinic. Asciminib binds to the myristate pocket of BCR-ABL1 and maintains… CONTINUE READING