The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1
Mar 22, 2017 · Here we characterize ABL001 (asciminib), a potent and selective allosteric ABL1 inhibitor that is undergoing clinical development testing in patients with CML and Philadelphia …
Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the ...
Aug 23, 2018 · 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 …
Multifunctional Abl kinases in health and disease - PMC
The BCR–ABL1 chimeric protein exhibits elevated tyrosine kinase and transforming activities, and has been identified in distinct human leukemias, including chronic myelogenous leukemia …
Mechanisms of Resistance to the BCR-ABL1 Allosteric Inhibitor …
We investigated mechanisms of asciminib resistance and identified two major categories: (1) upregulation of the ABCG2 efflux pump, resulting in undetectable intracellular asciminib levels, …
Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the ...
Sep 27, 2018 · 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 …
Mechanisms of resistance to the BCR-ABL1 allosteric inhibitor
Aug 18, 2017 · The BCR-ABL1 M244V/A337V compound mutant confers high-level asciminib resistance but inclusion of clinically achievable concentrations of imatinib lead to outgrowth of …
ABL001, a Potent Allosteric Inhibitor of BCR-ABL, Prevents …
Dec 6, 2014 · ABL001 is a potent, selective BCR-ABL inhibitor that maintains activity across most mutations, including T315I, with a distinct, allosteric mechanism of action which recently …
Asciminib antagonizes transplantable BCR::ABL1-positive …
Asciminib (ABL001) is a novel selective allosteric inhibitor of the ABL kinase with high efficacy against TKI-resistant BCR::ABL1. In this study, we demonstrate significant suppression of an …
Crystallography studies showed that ABL001 and nilotinib can co-bind a single molecule of BCR–ABL1 (Fig. 2a), and in vitro studies revealed additive effects of ABL001 in combination …
Dual BCR::ABL1 Inhibition Shows Promise in Philadelphia …
Apr 14, 2025 · A breakthrough came in 2017 6 with the successful development of a novel class of BCR::ABL1 inhibitors. In its normal state, wild-type ABL1 remains inactive when its …