The resurgence of covalent drugs

By Juswinder Singh, R. Petter, T. Baillie, A. Whitty. 2011

1,626 citations recorded by the source corpus.

Subfields: Computational Theory and Mathematics, Molecular Biology, Organic Chemistry, Optimization & Training

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Citations in the corpus

Molecular Docking and Structure-Based Drug Design Strategies (2015, background): “Usually, covalent inhibitors bind to their molecular targets with high affinity, leading to a long-lasting pharmacological response, and consequently requiring less frequent administration [89].”
Ligand–receptor interaction platforms and their applications for drug discovery (2012, background): “Examining the molecular and physiochemical properties of marketed drugs has highlighted the importance of the biochemical mechanisms of action including structural, kinetic, and thermodynamic signatures of drugs for their in vivo clinical performance [18-27].”
Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker (2012, background): “Newer chemical entities targeting ErbB receptors were designed to covalently engage their targets characterized by cysteine residues in the active site, assuming that this might translate into higher selectivity and longer residence time and, ultimately, into better efficacy (Copeland et al., 2006; ”
Kinase-targeted cancer therapies: progress, challenges and future directions (2018, background): “This type of kinase inhibition takes place via trapping of a solvent-exposed cysteine residue either by SN2 displacement of a leaving group or by reacting with a Michael acceptor incorporated within the kinase inhibitor [113, 120, 121].”
Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations (2017, background): “168 Although molecular mechanics force ﬁ elds cannot calculate the energetics of covalent bond formation, free energy simulations can still be used in such situations by analyzing only the noncovalent interactions, although the accuracy of such predictions depends on the fundamental assumption that…”
CavityPlus: a web server for protein cavity detection with pharmacophore modelling, allosteric site identification and covalent ligand binding ability prediction (2018, background): “About one third of the FDA approved drugs have been reported to act through covalent mechanisms (7,8).”
The design and development of covalent protein-protein interaction inhibitors for cancer treatment (2020, background): “In the 1970s, researchers reported that covalent drugs produce hepatotoxicity resulting from off-target effects via unselectively modifying non-target proteins with their highly reactive groups [37, 45].”