Results 1 to 10 of about 13,776 (87)
Reactivity of Covalent Fragments and Their Role in Fragment Based Drug Discovery
Pharmaceuticals, 2022 Fragment based drug discovery has long been used for the identification of new ligands and interest in targeted covalent inhibitors has continued to grow in recent years, with high profile drugs such as osimertinib and sotorasib gaining FDA approval.
Kirsten McAulay +2 more
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Characterization of the Second-Generation Covalent Fragment Library (CovLib Gen2): Thiol Reactivity Profiling and p53-Y220C Rescue [PDF]
Drug Design, Development and TherapyMartin Schwer,1 Sven R Aldea,1 Marc U Engelhardt,1 Jason Stahlecker,1 Janosch Rheinganz,1 Aaron Langkamp,1 Frank M Boeckler1,2 1Department of Pharmacy and Biochemistry, Laboratory for Molecular Design & Pharmaceutical Biophysics, Eberhard Karls ...
Schwer M +6 more
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Fragment‐based drug discovery—the importance of high‐quality molecule libraries
Molecular Oncology, 2022 Fragment‐based drug discovery (FBDD) is now established as a complementary approach to high‐throughput screening (HTS). Contrary to HTS, where large libraries of drug‐like molecules are screened, FBDD screens involve smaller and less complex molecules ...
Marta Bon +3 more
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A practical method for determining the rate of covalent modification of fragments and leads [PDF]
Nature CommunicationsThe clinical success of covalent drugs such as sotorasib has renewed interest in covalency for rational drug design. The most rigorous potency metric for covalent modifiers is the second-order rate constant k inact /K I.
Janice Jeon +5 more
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Covalent fragment-based drug discovery for target tractability
Current Opinion in Structural BiologyAn important consideration in drug discovery is the prioritization of tractable protein targets that are not only amenable to binding small molecules, but also alter disease biology in response to small molecule binding. Covalent fragment-based drug discovery has emerged as a powerful approach to aid in the identification of such protein targets.
Jacob T Bush +2 more
exaly +3 more sources
Covalent fragment inhibits intramembrane proteolysis
Frontiers in Molecular Biosciences, 2022 Alzheimer’s disease (AD) is a serious public health crisis with only one current modifying treatment. The reduction of amyloid load by targeting γ-secretase (GS) has been a leading approach in AD drug discovery and development.
Angela Eden +8 more
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Targeting the ubiquitin system by fragment-based drug discovery
Frontiers in Molecular Biosciences, 2022 The ubiquitin system contains a wealth of potential drug targets for many diseases and conditions, including neurodegenerative, immune, metabolic and developmental diseases, as well as multiple cancers.
Cassandra Kennedy +2 more
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Chemistry Proceedings, 2022 The search for new antibacterial drugs has continued to be an urgent matter. One of the approaches is the development of covalent inhibitors using biochemoinformatics at the initial stages.
Polina Yakovets +3 more
doaj +1 more source
Approach for the Design of Covalent Protein Kinase Inhibitors via Focused Deep Generative Modeling
Molecules, 2022 Deep machine learning is expanding the conceptual framework and capacity of computational compound design, enabling new applications through generative modeling.
Atsushi Yoshimori +2 more
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Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2
Nature Communications, 2023 The Src homology 2 (SH2) domain recognizes phosphotyrosine (pY) post translational modifications in partner proteins to trigger downstream signaling. Drug discovery efforts targeting the SH2 domains have long been stymied by the poor drug-like properties
Sarath Ramachandran +10 more
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