Perspectives on Applications of 19F-NMR in Fragment-Based Drug Discovery DOI Creative Commons
Qingxin Li, CongBao Kang

Molecules, Год журнала: 2024, Номер 29(23), С. 5748 - 5748

Опубликована: Дек. 5, 2024

Fragment-based drug discovery is a powerful approach in discovery, applicable to wide range of targets. This method enables the potent compounds that can modulate target functions, starting from fragment bind weakly While biochemical, biophysical, and cell-based assays are commonly used identify fragments,

Язык: Английский

NMR investigations of glycan conformation, dynamics, and interactions DOI
Jesús Angulo, Ana Ardá, Sara Bertuzzi

и другие.

Progress in Nuclear Magnetic Resonance Spectroscopy, Год журнала: 2024, Номер 144-145, С. 97 - 152

Опубликована: Окт. 12, 2024

Язык: Английский

Процитировано

4
Fragment Screening Identifies Novel Allosteric Binders and Binding Sites in the VHR (DUSP3) Phosphatase DOI Creative Commons
Jiaqian Wu, Marek R. Baranowski, Alexander E. Aleshin

и другие.

ACS Omega, Год журнала: 2025, Номер 10(5), С. 4912 - 4926

Опубликована: Янв. 31, 2025

The human Vaccinia H1-related phosphatase (VHR; DUSP3) is a critical positive regulator of the innate immune response. Recent studies suggest that inhibiting VHR could be beneficial in treating sepsis and septic shock. belongs to superfamily protein tyrosine phosphatases (PTPs), large class enzymes are notoriously difficult target with small molecules. Fragment-based drug discovery (FBDD) has emerged as an effective strategy for generating potent ligands, even challenging targets. Here, we present fluorine NMR-based platform identifying fragments bind VHR. This encompasses automated library assembly, mixture formation, quantitative material transfer, NMR screening, biophysical hit confirmation. We demonstrate this streamlined, integrated screening workflow produces validated hits diverse chemical matter tangible structure-activity relationships (SAR). Crystal structures yielded detailed information on fragment-protein interactions provide basis future structurally enabled ligand optimization. Notably, discovered novel binding sites VHR, distant from conserved active site, facilitating generation selective modulators. fragment can applied other PTPs holds significant potential ligands.

Язык: Английский

Процитировано

0
Synthesis and evaluation of fluorinated tetrahydrocarbazoles as probes in NMR based binding assay of the E. coli β sliding clamp DOI Creative Commons
Cecilie Elisabeth Olsen, Signe Simonsen,

Srinivas Reddy Merugu

и другие.

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер 122, С. 118139 - 118139

Опубликована: Фев. 27, 2025

Язык: Английский

Процитировано

0
Perspectives on Applications of 19F-NMR in Fragment-Based Drug Discovery DOI Creative Commons
Qingxin Li, CongBao Kang

Molecules, Год журнала: 2024, Номер 29(23), С. 5748 - 5748

Опубликована: Дек. 5, 2024

Fragment-based drug discovery is a powerful approach in discovery, applicable to wide range of targets. This method enables the potent compounds that can modulate target functions, starting from fragment bind weakly While biochemical, biophysical, and cell-based assays are commonly used identify fragments,

Язык: Английский

Процитировано

1