98%
921
2 minutes
20
A novel series of 2-aminobenzimidazole inhibitors of BACE1 has been discovered using fragment-based drug discovery (FBDD) techniques. The rapid optimization of these inhibitors using structure-guided medicinal chemistry is discussed.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.bmcl.2010.06.089 | DOI Listing |
Acc Chem Res
September 2025
Department of Pharmaceutical Chemistry and Small Molecule Discovery Center, University of California, San Francisco 94158, United States.
ConspectusProtein-protein interactions (PPIs) play a key role in homeostasis and are often dysregulated in disease. PPIs were traditionally considered "undruggable" due to their flat surfaces and disordered domains. Recently, the identification of PPI stabilizers, or molecular glues (MGs), compounds that bind cooperatively to PPI interfaces, has provided a new direction for the field.
View Article and Find Full Text PDFJ Comput Chem
September 2025
Johnson & Johnson, Beerse, Belgium.
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 screening workflow named FragmentScout, enable the advancement of novel antiviral agents. FragmentScout uses publicly accessible structural data of the SARS-CoV-2 NSP13 helicase, which was previously generated at the Diamond LightSource by XChem high-throughput crystallographic fragment screening.
View Article and Find Full Text PDFOrg Lett
August 2025
Department of Medicinal Chemistry, School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
Amidst nature's repertoire of small molecule architectures, indole alkaloid-derived privileged scaffolds continuously support innovation in bioactive compound discovery and propel fragment-based drug design. Herein, we realized a metal-free, site-selective, and chemo- and regioselective cross-nucleophile coupling cascade of pluripotent indole-enamine-aniline intermediates by use of λ-iodane-mediated umpolung chemistry. The protocol is applicable toward the divergent synthesis of valuable benzo[]indolo[3,2-][2,6]naphthyridines and azepino[4,5-]indoles, which are very important privileged scaffolds in communesin-, peroforamidine-, and iboga-type alkaloids.
View Article and Find Full Text PDFACS Chem Biol
August 2025
Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, 130 Scripps Way, Jupiter, Florida 33458, United States.
Fragment-based drug discovery typically relies on specialized spectrometric methods to identify low-affinity compounds that bind to biomolecules. Here, we report a proof-of-concept study on the development of a streamlined fragment-based screening platform for small molecules targeting RNA. This method employs low molecular weight fragments appended with a diazirine reactive moiety and an alkyne tag.
View Article and Find Full Text PDFJ Genet Eng Biotechnol
September 2025
Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail-1902, Bangladesh. Electronic address:
Antibiotic resistance poses a significant global challenge as bacteria evolve in response to antibiotic use, leading to prolonged hospitalizations, increased healthcare costs, and higher mortality rates. Cephalosporins, a class of beta-lactam antibiotics, are commonly employed to manage infections; however, their misuse and overuse have contributed to resistance development. In response, in silico methods have emerged as cost-effective and efficient tools for drug discovery.
View Article and Find Full Text PDF