Publications by authors named "Joshua A Ballard"
Article Synopsis
- Bruton tyrosine kinase (BTK) is important for treating B-cell cancers, but existing covalent inhibitors have issues with side effects and resistance mutations.
- Pirtobrutinib is a new, selective, noncovalent BTK inhibitor that effectively targets BTK and its mutations without the same drawbacks as current treatments.
- Preclinical studies show that pirtobrutinib not only inhibits B-cell lymphoma growth and signaling but also demonstrates improved selectivity and stability, leading to Phase 3 clinical trials for various B-cell malignancies.
Despite decades of research, efforts to directly target KRAS have been challenging. MRTX849 was identified as a potent, selective, and covalent KRAS inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRAS, and inhibits KRAS-dependent signaling. MRTX849 demonstrated pronounced tumor regression in 17 of 26 (65%) KRAS-positive cell line- and patient-derived xenograft models from multiple tumor types, and objective responses have been observed in patients with KRAS-positive lung and colon adenocarcinomas.
View Article and Find Full Text PDFThe protease activity of hepatitis C virus nonstructural protein 3 (NS3) is essential for viral replication. ITMN-191, a macrocyclic inhibitor of the NS3 protease active site, promotes rapid, multilog viral load reductions in chronic HCV patients. Here, ITMN-191 is shown to be a potent inhibitor of NS3 with a two-step binding mechanism.
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