Featured
-
-
Article
| Open Access
Lenalidomide derivatives and proteolysis-targeting chimeras for controlling neosubstrate degradation
Lenalidomide is effective for treating several hematological cancers but has teratogenic effect on the fetus. Here, the authors identify modifications that make lenalidomide more selective and effective when used as a stand-alone molecular glue or integrated in PROTACs.
- Satoshi Yamanaka
- , Hirotake Furihata
- & Tatsuya Sawasaki
-
Article
| Open Access
[2]-Ladderanes as isosteres for meta-substituted aromatic rings and rigidified cyclohexanes
The development of new classes of isosteres and building blocks is crucial to the advancement of medicinal chemistry programs. Here, the authors report the synthesis and development of ladderanes to act as replacements for meta-substituted aromatic rings and cyclohexanes.
- Rachel C. Epplin
- , Shashwati Paul
- & M. Kevin Brown
-
Article
| Open Access
Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19
Small molecule drugs promise to remain a valuable tool in controlling the ongoing COVID-19 pandemic. Here the authors describe optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for potential treatment of COVID-19.
- Hengrui Liu
- , Sho Iketani
- & Brent R. Stockwell
-
Article
| Open Access
Leveraging the multivalent p53 peptide-MdmX interaction to guide the improvement of small molecule inhibitors
Peptide fragments derived from the interfaces of protein-protein interactions (PPIs) provide useful templates for designing small molecule PPI inhibitors. Here, the authors utilize the multivalency of an MdmX-binding p53 peptide to develop a weak inhibitor of MdmX into potent Mdm2/MdmX inhibitors.
- Xiyao Cheng
- , Rong Chen
- & Zhengding Su
-
Article
| Open Access
Decisive role of water and protein dynamics in residence time of p38α MAP kinase inhibitors
The molecular determinants of the residence time of a small molecule inhibitor at its target protein are not well understood. Here, Pantsar et al. show that the target protein’s conformational stability and solvent exposure are key factors governing the target residence time of kinase inhibitors.
- Tatu Pantsar
- , Philipp D. Kaiser
- & Stefan A. Laufer
-
Article
| Open Access
A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A
The Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) is a component of commercial vaccines, but is unstable. Here, the authors generate glycomimetic oligomers that demonstrate higher stability than their natural counterparts and induce protective antibodies in mice.
- Jacopo Enotarpi
- , Marta Tontini
- & Roberto Adamo
-
Article
| Open Access
Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents
FK506 is a potential antifungal compound that inhibits calcineurin, but it also has immunosuppressive activity. Here, Juvvadi et al. report the structure of FK506 in complex with the FK506-binding protein FKPB12 and calcineurin, and design a less immunosuppresive FK506 analog with antifungal activity in mice.
- Praveen R. Juvvadi
- , David Fox III
- & William J. Steinbach
All-round catalytic and atroposelective strategy via dynamic kinetic resolution for N-/2-/3-arylindoles