Beyond cysteine: recent developments in the area of targeted covalent inhibition.
Sign Up to like & getrecommendations! Published in 2018 at "Current opinion in chemical biology"
DOI: 10.1016/j.cbpa.2018.05.011
Abstract: Over the past decade targeted covalent inhibitors have undergone a renaissance due to the clinical validation and regulatory approval of several small molecule therapeutics that are designed to irreversibly modify their target protein. Invariably, these… read more here.
Keywords: beyond cysteine; targeted covalent; area targeted; cysteine recent ... See more keywords
Combinatorially Screened Peptide as Targeted Covalent Binder: Alteration of Bait-Conjugated Peptide to Reactive Modifier.
Sign Up to like & getrecommendations! Published in 2018 at "Bioconjugate chemistry"
DOI: 10.1021/acs.bioconjchem.8b00301
Abstract: A peptide-type covalent binder for a target protein was obtained by combinatorial screening of fluoroprobe-conjugated peptide libraries on bacteriophage T7. The solvatochromic fluoroprobe works as a bait during the affinity selection process of phage display.… read more here.
Keywords: targeted covalent; conjugated peptide; bait; binder ... See more keywords
AI-Accelerated Design of Targeted Covalent Inhibitors for SARS-CoV-2
Sign Up to like & getrecommendations! Published in 2023 at "Journal of Chemical Information and Modeling"
DOI: 10.1021/acs.jcim.2c01377
Abstract: Direct-acting antivirals for the treatment of the COVID-19 pandemic caused by the SARS-CoV-2 virus are needed to complement vaccination efforts. Given the ongoing emergence of new variants, automated experimentation, and active learning based fast workflows… read more here.
Keywords: targeted covalent; covalent inhibitors; design targeted; accelerated design ... See more keywords
The Ascension of Targeted Covalent Inhibitors.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c02134
Abstract: Covalent drugs have made a major impact on human health but until recently were shunned by the pharmaceutical industry over concerns about the potential for toxicity. A resurgence has occurred driven by the clinical success… read more here.
Keywords: chemistry; ascension targeted; targeted covalent; covalent inhibitors ... See more keywords
Structure-Activity Relationships of Potent, Targeted Covalent Inhibitors That Abolish Both the Transamidation and GTP Binding Activities of Human Tissue Transglutaminase.
Sign Up to like & getrecommendations! Published in 2017 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.7b01070
Abstract: Human tissue transglutaminase (hTG2) is a multifunctional enzyme. It is primarily known for its calcium-dependent transamidation activity that leads to formation of an isopeptide bond between glutamine and lysine residues found on the surface of… read more here.
Keywords: human tissue; targeted covalent; tissue transglutaminase; gtp binding ... See more keywords
Structure-based design of targeted covalent inhibitors.
Sign Up to like & getrecommendations! Published in 2018 at "Chemical Society reviews"
DOI: 10.1039/c7cs00220c
Abstract: Covalent inhibition is a rapidly growing discipline within drug discovery. Many historical covalent inhibitors were discovered by serendipity, with such a mechanism of action often regarded as undesirable due to potential toxicity issues. Recent progress… read more here.
Keywords: covalent inhibitors; targeted covalent; covalent inhibition; covalent ... See more keywords
Allenamide as a bioisostere of acrylamide in the design and synthesis of targeted covalent inhibitors.
Sign Up to like & getrecommendations! Published in 2018 at "MedChemComm"
DOI: 10.1039/c7md00571g
Abstract: The success of acrylamide-containing drugs in treating cancers has spurred a passion to search for acrylamide bioisosteres. In our endeavour, we have identified that an allenamide group can be a reactive bioisostere of the acrylamide… read more here.
Keywords: bioisostere acrylamide; design synthesis; covalent inhibitors; targeted covalent ... See more keywords
Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides.
Sign Up to like & getrecommendations! Published in 2019 at "Chemical communications"
DOI: 10.1039/c9cc04022f
Abstract: Herein, we describe the development of a novel staple with an electrophilic warhead to enable the generation of stapled peptide covalent inhibitors of the p53-MDM2 protein-protein interaction (PPI). The peptide developed showed complete and selective… read more here.
Keywords: covalent inhibitors; targeted covalent; electrophile bearing; mdm2 using ... See more keywords
bioTCIs: Middle-to-Macro Biomolecular Targeted Covalent Inhibitors Possessing Both Semi-Permanent Drug Action and Stringent Target Specificity as Potential Antibody Replacements
Sign Up to like & getrecommendations! Published in 2023 at "International Journal of Molecular Sciences"
DOI: 10.3390/ijms24043525
Abstract: Monoclonal antibody therapies targeting immuno-modulatory targets such as checkpoint proteins, chemokines, and cytokines have made significant impact in several areas, including cancer, inflammatory disease, and infection. However, antibodies are complex biologics with well-known limitations, including… read more here.
Keywords: target; targeted covalent; drug action; drug ... See more keywords