A5049005810- Scientific Computing and Data Management
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Cell Image Analysis Techniques
- Space Science and Extraterrestrial Life
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Data Visualization and Analytics
- Epigenetics and DNA Methylation
- Computational Drug Discovery Methods
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Cancer-related gene regulation
- Computational Physics and Python Applications
Novartis (United States)
2023-2024
Novartis (China)
2023
WD repeat domain 5 (WDR5) is a member of the WD40-repeat protein family that plays critical role in multiple processes. It also prominent target for pharmacological inhibition diseases such as cancer, aging, and neurodegenerative disorders. Interactions between WDR5 various partners are essential sustaining its function. Most drug discovery efforts center on WIN (WDR5 interaction motif) site responsible recruitment to chromatin. Here, we describe novel inhibitors other WBM binding pocket...
Abstract We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized three-dimensional (3D) modeling method Pocket2Mol, for de novo design of molecules spatial perspective targeted protein structures, followed by filters chemical-physical properties and drug-likeness, structure–activity relationship analysis, clustering generate top virtual scaffolds. In our WDR5...
WDR5 is a critical chromatin cofactor of MYC. interacts with MYC through the WBM pocket and hypothesized to anchor its WIN site. Blocking interaction impairs recruitment target genes disrupts oncogenic function in cancer development, thus providing promising strategy for treatment MYC-dysregulated cancers. Here, we describe discovery novel antagonists containing 1-phenyl dihydropyridazinone 3-carboxamide core that was identified from high-throughput screening subsequent structure-based...
Drug resistance is a major problem often limiting the long-term effectiveness of targeted cancer therapeutics. Resistance can be acquired through mutations or amplification primary drug targets activation bypass signaling pathways. Considering multifaceted function WDR5 in human malignancies, has emerged as an attractive target for discovery small-molecule inhibitors. In this study, we investigated if cells might develop to highly potent inhibitor. We established drug-adapted cell line and...
We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized 3D (three-dimensional) modeling method, e.g. Pocket2Mol, for de novo design of molecules spatial perspective targeted protein structures, followed by filters chemical-physical properties and drug-likeness, SAR (structure-activity relationship) analysis, clustering generate top virtual scaffolds. In our...