Chris Asquith

Hitting the target! Here is our recent review in Euro J Med Chem highlighting the uses and advantages of the very versatile Dimroth Rearrangement in both drug discovery and process chemistry.
@uniuef.bsky.social, @elsevierconnect.bsky.social, #chemsky - Check it out - doi.org/10.1016/j.ej...

Here is our new publication reviewing medicinal chemistry applications of the Dimroth Rearrangement in drug discovery. - check it out in Euro J Med Chem - doi.org/10.1016/j.ej...

Report: Every dollar of NIH research funding doubles in economic returns Research funded by the National Institutes of Health (NIH) generated $2.46 in economic activity for every $1 of funding in 2023, a total of $92.9 billion, according to an

www.fiercebiotech.com/research/rep...

Engineering covalent small molecule–RNA complexes in living cells - Nature Chemical Biology Small-molecule ligands have been developed that covalently attach to their cognate RNA aptamers in vitro and in living cells. This strategy opens up new avenues for RNA imaging applications (for examp...

A new paper reports the engineering of small-molecule ligands that covalently attach to their cognate RNA aptamers in vitro and in living cells

www.nature.com/articles/s41...

Engineering and structures of Crimean-Congo hemorrhagic fever virus glycoprotein complexes Crimean-Congo hemorrhagic fever virus is a widespread tickborne virus that infects humans. Engineering-based structural studies of the viral glycoprotein complexes GP38-Gn and GP38-Gn-Gc provide insights to their function in the viral life cycle. GP38-Gn-Gc confers partial protection against lethal viral challenge in mice, showing promise as a vaccine antigen for further development.

Nice work from @mclellanlab.bsky.social 👇🏼

"Engineering and structures of Crimean-Congo hemorrhagic fever virus glycoprotein complexes"

www.cell.com/cell/fulltex...

Guardians at the Gate: Optimization of Small Molecule Entry Inhibitors of Ebola and Marburg Viruses Ebola and Marburg (EBOV and MARV) filoviral infections lead to fatal hemorrhagic fevers and have caused over 30 outbreaks in the last 50 years. Currently, there are no FDA-approved small molecule therapeutics for effectively treating filoviral diseases. To address this unmet medical need, we have conducted a systematic structural optimization of an early lead compound, N-(4-(4-methylpiperidin-1-yl)-3-(trifluoromethyl)phenyl)-4-(morpholinomethyl)benzamide (1), borne from our previously reported hit-to-lead effort. This secondary round of structure–activity relationship (SAR) involved the design and synthesis of several deconstructed and reconstructed analogs of compound 1, which were then tested against pseudotyped EBOV and MARV. The antiviral activities of the most promising leads were further validated in infectious assays. The optimized analogs exhibited desirable antiviral activity against different ebolaviruses and reduced off-target activity. Additionally, they also possessed druglike properties, that make them ideal candidates for in vivo efficacy studies as part of our ongoing drug discovery campaign against EBOV and MARV.

Interesting design of new ebola/marburg virus inhibitors pubs.acs.org/doi/10.1021/...

The impact of library size and scale of testing on virtual screening - Nature Chemical Biology The docking of a 1.7 billion- versus a 99 million-molecule virtual library against β-lactamase revealed that the larger-sized library produced improved hit rates and potency along with an increased nu...

The docking of a 1.7 billion- vs a 99 million-molecule virtual library against β-lactamase reveals that the larger-sized library produced improved hit rates and potency along with an increased number of scaffolds. #ChemBio #chemsky #compchem

www.nature.com/articles/s41...

Chemical tools to expand the ligandable proteome: Diversity-oriented synthesis-based photoreactive stereoprobes Many human proteins lack chemical probes and are even considered undruggable. Ogasawara et al. describe diversity-oriented synthesis-inspired photoreactive small molecules (photo-stereoprobes) and the...

Cool paper from Cravatt lab: Chemical tools to expand the ligandable proteome: Diversity-oriented synthesis-based photoreactive stereoprobes: www.cell.com/cell-chemica...