A5048100642- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Multiple Myeloma Research and Treatments
- Cell death mechanisms and regulation
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Metabolomics and Mass Spectrometry Studies
- Computational Drug Discovery Methods
- Microbial Natural Products and Biosynthesis
University of Michigan
2022
Development of B-cell lymphoma 2 (BCL-2)-specific inhibitors poses unique challenges in drug design because BCL-2 homology domain 3 (BH3) shared between family members and the shallow surface their protein-protein interactions. We report herein discovery extensive preclinical investigation lisaftoclax (APG-2575).Computational modeling was used to "lead" compounds. Biochemical binding, mitochondrial BH3 profiling, cell-based viability or apoptosis assays were determine selectivity potency...
Characterizing the kinome selectivity profiles of kinase inhibitors is essential in early stages novel small-molecule drug discovery. This characterization critical for interpreting potential adverse events caused by off-target polypharmacology effects and provides unique pharmacological insights repurposing development existing inhibitor drugs. However, experimental profiling whole still time-consuming resource-demanding. Here, we report a deep learning classification model using an...
Supplementary Figures from Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy
Supplementary Data from Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy
<div>AbstractPurpose:<p>Development of B-cell lymphoma 2 (BCL-2)–specific inhibitors poses unique challenges in drug design because BCL-2 homology domain 3 (BH3) shared between family members and the shallow surface their protein–protein interactions. We report herein discovery extensive preclinical investigation lisaftoclax (APG-2575).</p>Experimental Design:<p>Computational modeling was used to “lead” compounds. Biochemical binding, mitochondrial BH3 profiling,...
<div>AbstractPurpose:<p>Development of B-cell lymphoma 2 (BCL-2)–specific inhibitors poses unique challenges in drug design because BCL-2 homology domain 3 (BH3) shared between family members and the shallow surface their protein–protein interactions. We report herein discovery extensive preclinical investigation lisaftoclax (APG-2575).</p>Experimental Design:<p>Computational modeling was used to “lead” compounds. Biochemical binding, mitochondrial BH3 profiling,...
Supplementary Figures from Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy
Supplementary Data from Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy