Fragment‐based drug discovery—the importance of high‐quality molecule libraries
Sign Up to like & getrecommendations! Published in 2022 at "Molecular Oncology"
DOI: 10.1002/1878-0261.13277
Abstract: Fragment‐based drug discovery (FBDD) is now established as a complementary approach to high‐throughput screening (HTS). Contrary to HTS, where large libraries of drug‐like molecules are screened, FBDD screens involve smaller and less complex molecules which,… read more here.
Keywords: fragment based; drug discovery; based drug; discovery importance ... See more keywords
Fragment‐Based Design, Synthesis, and Biological Evaluation of 1‐Substituted‐indole‐2‐carboxylic Acids as Selective Mcl‐1 Inhibitors
Sign Up to like & getrecommendations! Published in 2017 at "Archiv der Pharmazie"
DOI: 10.1002/ardp.201600251
Abstract: Based on a known selective Mcl‐1 inhibitor, 6‐chloro‐3‐(3‐(4‐chloro‐3,5‐dimethylphenoxy)propyl)‐1H‐indole‐2‐carboxylic acid, we applied a fragment‐based approach to obtain new molecules that extended into the p1 pocket of the BH3 groove and then exhibited binding selectivity for the… read more here.
Keywords: mcl; indole carboxylic; selective mcl; fragment based ... See more keywords
Development of Urease Inhibitors by Fragment‐Based Dynamic Combinatorial Chemistry
Sign Up to like & getrecommendations! Published in 2022 at "ChemMedChem"
DOI: 10.1002/cmdc.202200307
Abstract: In this study, fragment‐based dynamic combinatorial chemistry (DCC) was explored for the development of novel urease inhibitors. Based on a rationally designed fragment, two iteratively evolved dynamic combinatorial libraries (DCLs) were generated and screened in… read more here.
Keywords: fragment based; dynamic combinatorial; combinatorial chemistry; chemistry ... See more keywords
Fragment‐Based Design, Synthesis, and Characterization of Aminoisoindole‐Derived Furin Inhibitors
Sign Up to like & getrecommendations! Published in 2024 at "ChemMedChem"
DOI: 10.1002/cmdc.202400057
Abstract: A 1H‐isoindol‐3‐amine was identified as suitable P1 group for the proprotein convertase furin using a crystallographic screening with a set of 20 fragments known to occupy the S1 pocket of trypsin‐like serine proteases. Its binding… read more here.
Keywords: derived furin; furin; benzamidine derived; fragment based ... See more keywords
A New Fragment‐Based Pharmacophore Virtual Screening Workflow Identifies Potent Inhibitors of SARS‐CoV‐2 NSP13 Helicase
Sign Up to like & getrecommendations! Published in 2025 at "Journal of Computational Chemistry"
DOI: 10.1002/jcc.70201
Abstract: Herein we report the in silico discovery of 13 novel micromolar potent inhibitors of the SARS‐CoV‐2 NSP13 helicase validated in cellular antiviral and biophysical ThermoFluor assays. The compounds, discovered using a novel fragment‐based pharmacophore virtual… read more here.
Keywords: sars cov; screening workflow; fragment based; fragment ... See more keywords
Fragment-based drug design targeting syntenin PDZ2 domain involved in exosomal release and tumour spread.
Sign Up to like & getrecommendations! Published in 2021 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2021.113601
Abstract: Syntenin stimulates exosome production and its expression is upregulated in many cancers and implicated in the spread of metastatic tumor. These effects are supported by syntenin PDZ domains interacting with syndecans. We therefore aimed to… read more here.
Keywords: syntenin pdz2; targeting syntenin; fragment based; drug design ... See more keywords
Discovery of novel TMPRSS2 inhibitors for COVID-19 using in silico fragment-based drug design, molecular docking, molecular dynamics, and quantum mechanics studies
Sign Up to like & getrecommendations! Published in 2022 at "Informatics in Medicine Unlocked"
DOI: 10.1016/j.imu.2022.100870
Abstract: The global expansion of COVID-19 and the mutations of severe acute respiratory syndrome coronavirus necessitate quick development of treatment and vaccination. Because the androgen-responsive serine protease TMPRSS2 is involved in cleaving the SARS-CoV-2 spike protein… read more here.
Keywords: tmprss2; mechanics; fragment based; drug design ... See more keywords
Small Glycols Discover Cryptic Pockets on Proteins for Fragment-Based Approaches
Sign Up to like & getrecommendations! Published in 2021 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.0c01126
Abstract: Cryptic pockets are visible in ligand-bound protein structures but are occluded in unbound structures. Utilizing these pockets in fragment-based drug-design provides an attractive option for proteins not tractable by classical binding sites. However, owing to… read more here.
Keywords: fragment based; small glycols; cryptic pocket; pocket ... See more keywords
Exploration of Chemical Space Guided by PixelCNN for Fragment-Based De Novo Drug Discovery
Sign Up to like & getrecommendations! Published in 2022 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.2c01345
Abstract: We report a novel framework for achieving fragment-based molecular design using pixel convolutional neural network (PixelCNN) combined with the simplified molecular input line entry system (SMILES) as molecular representation. While a widely used recurrent neural… read more here.
Keywords: fragment based; chemical space; chemical; exploration chemical ... See more keywords
Quick-and-Easy Validation of Protein-Ligand Binding Models Using Fragment-Based Semiempirical Quantum Chemistry
Sign Up to like & getrecommendations! Published in 2025 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.4c01987
Abstract: Electronic structure calculations in enzymes converge very slowly with respect to the size of the model region that is described using quantum mechanics (QM), requiring hundreds of atoms to obtain converged results and exhibiting substantial… read more here.
Keywords: chemistry; fragment based; protein ligand; model ... See more keywords
Improved Electrostatic Embedding for Fragment-Based Chemical Shift Calculations in Molecular Crystals.
Sign Up to like & getrecommendations! Published in 2017 at "Journal of chemical theory and computation"
DOI: 10.1021/acs.jctc.7b00677
Abstract: Fragment-based methods predict nuclear magnetic resonance (NMR) chemical shielding tensors in molecular crystals with high accuracy and computational efficiency. Such methods typically employ electrostatic embedding to mimic the crystalline environment, and the quality of the… read more here.
Keywords: electrostatic embedding; molecular crystals; fragment based; chemical shift ... See more keywords