Journal of Pharmaceutical Sciences, Journal Year: 2023, Volume and Issue: 113(3), P. 539 - 554
Published: Nov. 4, 2023
Language: Английский
Biologie Aujourd hui, Journal Year: 2024, Volume and Issue: 218(1-2), P. 41 - 54
Published: Jan. 1, 2024
The review is focused on recent drug discovery advances based targeted protein degradation strategies. This new area of research has exploded leading to the development potential drugs useful in a large variety human diseases. They first target disease relevant proteins difficult counteract with other classical strategies and extend now aggregates, organelles, nucleic acids or lipidic droplets. These degraders engaged either ubiquitin-proteasome system for PROTACs molecular glues (first generation), lysosomal via endosome-lysosome (LYTACs) autophagy-lysosome (ATTEC, AUTAC, AUTOTAC) (following generations degraders). have expanded from orthodox heterobifunctional ones derivatives such as homo-PROTACs, pro-PROTACs, CLIPTACs, HaloPROTACs, PHOTOTACs, Bac-PROTACs, AbTACs, ARN-PROTACs. small molecular-weight induce formation ternary complexes which implicate an ubiquitin ligase E3 allowing ubiquinitation followed by its proteasomal degradation. Lysosomal (LYTAC, ATTEC, specifically recognize extracellular membrane dysfunctional organelles transport them into lysosomes where they are degraded. overcome limitations observed degradations induced PROTAC demonstrate their treat diseases, especially neurodegenerative ones. Pharmaceutical companies at world level develop these targeting cancers, immuno-inflammatory diseases well Efficiency risks novel therapeutic discussed.
Language: Английский
Citations
0
Chemical Science, Journal Year: 2024, Volume and Issue: 15(36), P. 14625 - 14634
Published: Jan. 1, 2024
Mitochondrial-targeted protein degradation (mitoTPD) is explored using small-molecule degraders that leverage a mitochondria-localized protease. This approach restored mitochondrial morphology and shows potential for drug discovery.
Language: Английский
Citations
0
Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 366(2), P. 269 - 276
Published: Nov. 30, 2023
Abstract Here we present a [3+2] cycloaddition of rationally designed trisubstituted cyclic α‐chloroamides, primarily those incorporating pharmacological pyrazolone cores, as potent synthons for synthesizing valuable spirocyclic γ‐lactam architectures. This protocol exhibits 52–96% yields, impressive substrate compatibility, and scale‐up capacity. Importantly, this study also represents one the rare examples that harness enaminone C−N bond cleavage to engineer relevant skeletons biological interest. Moreover, propose plausible mechanistic explanation elucidate outstanding chemical outcomes observed, thereby enriching synthetic toolbox chemistry α‐haloamide‐mediated reactions.
Language: Английский
Citations
1
Artificial Intelligence Chemistry, Journal Year: 2023, Volume and Issue: 1(2), P. 100022 - 100022
Published: Oct. 24, 2023
The LC3 proteins play a crucial role in autophagy by participating to the formation of autophagosome. Modulation molecular interference with could help understand this complex fundamental biological process and how it is involved several pathologies. Identifying new ligands useful contribution aim. In present study, we created PubChem library 749 compounds having structure based on central scaffold novobiocin, reported LC3A ligand. A robust, rapid exhaustive algorithm was used for docking each compound database as within dihydronovobiocin binding site, providing score. Remarkable reliability consistency between scores efficiencies known observed, validating machine leaning protocol study. Investigation mode best score provides additional insights possible actions identified ligands.
Language: Английский
Citations
0
Journal of Pharmaceutical Sciences, Journal Year: 2023, Volume and Issue: 113(3), P. 539 - 554
Published: Nov. 4, 2023
Language: Английский
Citations
0