A5065328377- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
University of Perugia
2022-2024
Hetero-bifunctional PROteolysis TArgeting Chimeras (PROTACs) represent a new emerging class of small molecules designed to induce polyubiquitylation and proteasomal-dependent degradation target protein. Despite the increasing number publications about synthesis, biological evaluation, mechanism action PROTACs, characterization pharmacokinetic properties this compounds is still minimal. Here, we report study on metabolism series 40 PROTACs in cryopreserved human hepatocytes at multiple time...
Proteolysis targeting chimeras (PROTACs) represent an emerging class of compounds for innovative therapeutic application. Their bifunctional nature induces the formation a ternary complex (target protein/PROTAC/E3 ligase) which allows target protein ubiquitination and subsequent proteasomal-dependent degradation. To date, despite great efforts being made to improve their biological efficacy PROTACs rational design still represents challenging task, above all modulation physicochemical...
PROteolysis TArgeting Chimeras (PROTACs) are tripartite molecules consisting of a linker connecting ligand for protein interest to an E3 ligase recruiter, whose rationale relies on proteasome-based degradation. PROTACs have expanded as therapeutic strategy open new avenues unmet medical needs. Leveraging our expertise, we undertook series in vitro experiments aimed at elucidating PROTAC metabolism. In particular, focused recruiting the von Hippel-Lindau (VHL) ligase. After high-resolution...
Emerging drug candidates more often fall in the beyond-rule-of-five chemical space. Among them, proteolysis targeting chimeras (PROTACs) have gained great attention past decade. Although physicochemical properties of small molecules accomplishing Lipinski's rule-of-five can now be easily predicted through models generated by large data collections, for PROTACs knowledge is still limited and heterogeneous, hampering their prediction. Here, kinetic solubility coefficient distribution at pH 7.4 (LogD
Selective degradation of disease-causing proteins using proteolysis targeting chimeras (PROTACs) has gained great attention, thanks to its several advantages over traditional therapeutic modalities.