Kinases Controlling Stability of the Oncogenic MYCN Protein.

We previously identified the natural products isopomiferin and pomiferin as powerful, indirect MYCN-ablating agents. In this work, we expand on their mechanism of action and find that casein kinase 2 (CK2), phosphoinositide 3-kinase (PI3K), checkpoint kinase 1 (CHK1) and serine/threonine protein kinase 38-like (STK38L), as well as STK38, work synchronously to create a field effect that maintains MYCN stability. By systematically inhibiting these kinases, we degraded MYCN and induced cell death.

Use of Therapeutic Apheresis methods in ICU.

Apheresis is a modern medical approach in which plasma or cellular components are separated from the whole blood. Apheresis can be either diagnostic or therapeutic. Diagnostic apheresis is typically applied in hematology and cancer research.

Small-molecule allosteric inhibitors of GPX4.

Encouraged by the dependence of drug-resistant, metastatic cancers on GPX4, we examined biophysical mechanisms of GPX4 inhibition, which revealed an unexpected allosteric site. We found that this site was involved in native regeneration of GPX4 under low glutathione conditions. Covalent binding of inhibitors to this allosteric site caused a conformational change, inhibition of activity, and subsequent cellular GPX4 protein degradation.

Apheresis and COVID-19 in intensive care unit (ICU).

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, and on March 2020 the World Health Organization (WHO) declared it as pandemic, causing a public health crisis.

Cascade aza-Wittig/6π-Electrocyclization in the Synthesis of 1,6-Dihydropyridines.

A metal-free protocol for the synthesis of substituted 1,6-dihydropyridines with quaternary stereogenic centers via a cascade aza-Wittig/6π-electrocyclization process has been developed. The high functional group compatibility and broad scope of this method were demonstrated by using a wide range of easily available vinyliminophosphoranes and ketones, with yields up to 97%. A modification of the obtained products allowed for an increase in complexity and chemical diversity.

Catalytic Selective Metal-Free Cross-Coupling of Heteroaromatic N-Oxides with Organosilanes.

A metal-free, regioselective C-H functionalization of heteroaromatic N-oxides has been developed. The method enables the synthesis of various benzylated and alkynylated N-heterocycles in a transition-metal-free manner employing organosilanes as coupling partners. The unanticipated reactivity has been exploited for the synthesis of a number of symmetrical disubstituted acetylenes from ethynyltrimethylsilane via carbon-silicon bond metathesis.