Peptide‐based covalent inhibitors of protein–protein interactions
Sign Up to like & getrecommendations! Published in 2022 at "Journal of Peptide Science"
DOI: 10.1002/psc.3457
Abstract: Protein–protein interactions (PPI) are involved in all cellular processes and many represent attractive therapeutic targets. However, the frequently rather flat and large interaction areas render the identification of small molecular PPI inhibitors very challenging. As… read more here.
Keywords: peptide based; inhibitors protein; protein protein; based covalent ... See more keywords
Discovery of Michael acceptor containing 1,4-dihydropyridines as first covalent inhibitors of L-/T-type calcium channels.
Sign Up to like & getrecommendations! Published in 2019 at "Bioorganic chemistry"
DOI: 10.1016/j.bioorg.2019.103187
Abstract: 1,4-Dihydropyridines (DHPs) are an important class of blockers targeting different calcium channel subtypes and have great therapeutic value against cardiovascular and neurophysiologic conditions. Here, we present the design of DHP-based hexahydroquinoline derivatives as either selective… read more here.
Keywords: covalent inhibitors; calcium channels; type calcium; michael acceptor ... See more keywords
Sticking it to KRAS: Covalent Inhibitors Enter the Clinic.
Sign Up to like & getrecommendations! Published in 2020 at "Cancer cell"
DOI: 10.1016/j.ccell.2019.12.009
Abstract: Drugs that target KRAS 12C covalently, AMG 510 and MRTX849, are now in the clinic. Recent papers describe development of these compounds, their selectivity and properties, early clinical data, and potential combination therapies. These papers… read more here.
Keywords: sticking kras; covalent inhibitors; inhibitors enter; enter clinic ... See more keywords
Identification of covalent inhibitors that disrupt M. tuberculosis growth by targeting multiple serine hydrolases involved in lipid metabolism.
Sign Up to like & getrecommendations! Published in 2021 at "Cell chemical biology"
DOI: 10.1016/j.chembiol.2021.08.013
Abstract: The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their importance for the synthesis… read more here.
Keywords: covalent inhibitors; identification covalent; serine hydrolases; tuberculosis growth ... See more keywords
Structure-based design of covalent inhibitors targeting metallo-β-lactamases.
Sign Up to like & getrecommendations! Published in 2020 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2020.112573
Abstract: The emergence and prevalence of metallo-β-lactamases (MβLs)-mediated bacterial resistance has seriously threatened the global health today. MβLs are deemed to be one of the most worrying bacterial resistance factors that hydrolyze nearly all β-lactam antibiotics.… read more here.
Keywords: covalent inhibitors; design covalent; covalent; metallo lactamases ... See more keywords
The art of suicidal molecular seduction for targeting drug resistance.
Sign Up to like & getrecommendations! Published in 2020 at "Medical hypotheses"
DOI: 10.1016/j.mehy.2020.109676
Abstract: The development of drug resistance is one of the most significant challenges of the current century in the pharmaceutical industry. Superinfections, cancer chemoresistance, and resistance observed in many non-infectious diseases are nullifying the efforts and… read more here.
Keywords: drug resistance; covalent inhibitors; drug; resistance ... See more keywords
Affinity and Selectivity Assessment of Covalent Inhibitors by Free Energy Calculations
Sign Up to like & getrecommendations! Published in 2020 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.0c00834
Abstract: Covalent inhibitors have been gaining increased attention in drug discovery due to their beneficial properties such as long residence time, high biochemical efficiency, and specificity. Optimization of covalent inhibitors is a complex task that involves… read more here.
Keywords: selectivity; covalent inhibitors; free energy; energy calculations ... 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
MD-Based Assessment of Covalent Inhibitors in Noncovalent Association Complexes: Learning from Cathepsin K as a Test Case
Sign Up to like & getrecommendations! Published in 2023 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.3c00061
Abstract: A sufficiently stable noncovalent association complex between a covalent inhibitor and its protein target is regarded as a prerequisite for the formation of a covalent complex. As this transient form can hardly be assessed experimentally,… read more here.
Keywords: cathepsin; covalent inhibitors; covalent; based assessment ... See more keywords
Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of Candidiasis.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c02102
Abstract: Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors of FBA from Candida… read more here.
Keywords: bisphosphate aldolase; covalent; covalent inhibitors; covalent allosteric ... 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