ABSTRACT
Formyl peptide receptors (FPRs) comprise a class of chemoattractant pattern recognition receptors, for which several physiological functions like host-defences, as well as the regulation of inflammatory responses, have been ascribed. With accumulating evidence that agonism of FPR1/FPR2 can confer pro-resolution of inflammation, increased attention from academia and industry has led to the discovery of new and interesting small-molecule FPR1/FPR2 agonists. Focused attention on the development of appropriate physicochemical and pharmacokinetic profiles is yielding synthesis of new compounds with promising in vivo readouts. This review presents an overview of small-molecule FPR1/FPR2 agonist medicinal chemistry developed over the past 20 years, with a particular emphasis on interrogation in the increasingly sophisticated bioassays which have been developed.
Subject(s)
Anti-Inflammatory Agents , Neutrophils , Receptors, Formyl Peptide , Receptors, Formyl Peptide/agonists , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacologyABSTRACT
ICBS 2022 was a refreshing multi-day event where it was justified that the advancement of chemical biology did not halt due to the pandemic, but in contrast, amazing findings were discovered within the restrictions of the SARS-CoV-2 pandemic. All aspects of this annual gathering reinforced that interconnecting the branches of chemical biology through collaboration, the sharing of ideas and knowledge, and networking are enabling the discovery and diversification of applications that will arm scientists of this world in "uncovering solutions for diseases."
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , PandemicsABSTRACT
Here, we describe our action plan for hit identification (APHID) that guides the process of hit triage, with elimination of less tractable hits and retention of more tractable hits. We exemplify the process with reference to our high-throughput screening (HTS) campaign against the enzyme, KAT6A, that resulted in successful identification of a tractable hit. We hope that APHID could serve as a useful, concise and digestible guide for those involved in HTS and hit triage, especially those that are relatively new to this exciting and continually evolving technology.
Subject(s)
Enzyme Inhibitors/pharmacology , High-Throughput Screening Assays , Histone Acetyltransferases/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Histone Acetyltransferases/metabolism , Humans , Molecular StructureABSTRACT
The construction of intermolecular C-C, C-O, C-S and C-N bonds between diazo compounds and acyclic and cyclic 1,3-dicarbonyl compounds, thiophenol and alkynes was developed by using TFMSA@SBA-15, thus providing a metal-free and eco-friendly platform for forging those chemical bonds.
