Absztrakt Identifying genes with prognostic significance that can act as biomarkers in solid tumors can help stratify patients and uncover novel therapy targets. Here, our goal was to expand our previous ranking analysis of survival-associated genes in various solid tumors to include colon…
Absztrakt The clinical success of PARP1/2 inhibitors (PARPi) prompts the expansion of their applicability beyond homologous recombination deficiency. Here, we demonstrate that the loss of the accessory subunits of DNA polymerase epsilon, POLE3 and POLE4, sensitizes cells to PARPi. We…
Absztrakt Complement is an ancient and complex network of the immune system and, as such, it plays vital physiological roles, but it is also involved in numerous pathological processes. The proper regulation of the complement system is important to allow…
Absztrakt A propylphosphonic anhydride (T3P®)-mediated new multicomponent method was developed for the synthesis of benzo[de]isoquinolinones bearing a phosphonate or a phosphine oxide moiety as a new family of compounds. The one-pot three-component reaction of 1,8-naphthalaldehydic acid, primary amines and dialkyl…
Absztrakt A series of new dialkyl α-diethylphosphonoylethyl-α-hydroxy-ethylphosphonates were prepared using the Pudovik reaction of the corresponding γ-oxophosphonate with dialkyl phosphites performed on the surface of Al2O3 The adducts revealed unexpected reactivity in the attempted O-acylation reaction, and provided the corresponding…
Absztrakt DNA damage tolerance (DDT) pathways mitigate the effects of DNA damage during replication by rescuing the replication fork stalled at a DNA lesion or other barriers and also repair discontinuities left in the newly replicated DNA. From yeast to mammalian…
Absztrakt Screening of ultra-low-molecular weight ligands (MiniFrags) successfully identified viable chemical starting points for a variety of drug targets. Here we report the electrophilic analogues of MiniFrags that allow the mapping of potential binding sites for covalent inhibitors by biochemical…
Absztrakt Covalent inhibition has been attracting significant attention in drug discovery. Here we present the free energy-based computational modeling of both reversible and irreversible covalent inhibitors. The specific features of reversible inhibition are discussed emphasizing the difference between the two-state…
Absztrakt Heterocyclic thiones have recently been identified as reversible covalent warheads, consistent with their mild electrophilic nature. Little is known so far about their mechanism of action in labelling nucleophilic sidechains, especially cysteines. The vast number of tractable cysteines promotes…
Absztrakt The increasing role of the DNA-encoded library technology in early phase drug discovery represents a significant demand for DNA-compatible synthetic methods for therapeutically relevant heterocycles. Herein, we report the first on-DNA synthesis of multisubstituted indoles via a cascade reaction…