Results 51 to 60 of about 13,822,676 (240)

Selective DNA Gyrase Inhibitors: Multi-Target in Silico Profiling with 3D-Pharmacophores

Pharmaceuticals, 2021
DNA gyrase is an important target for the development of novel antibiotics. Although ATP-competitive DNA gyrase (GyrB) inhibitors are a well-studied class of antibacterial agents, there is currently no representative used in therapy, largely due to ...
Tihomir Tomašič, Asta Zubrienė, Žiga Skok, Riccardo Martini, Stane Pajk, Izidor Sosič, Janez Ilaš, Daumantas Matulis, Sharon D. Bryant   +8 more
doaj   +1 more source

Pharmacophore-Based Design of New Chemical Scaffolds as Translational Readthrough-Inducing Drugs (TRIDs)

, 2020
Translational readthrough-inducing drugs (TRIDs) rescue the functional full-length protein expression in genetic diseases, such as cystic fibrosis, caused by premature termination codons (PTCs).
Raffaella Melfi (463474), Ambra Campofelice (8473557), Anna Maria Almerico (1965865), Laura Lentini (84238), Giulia Culletta (8473560), Andrea Pace (1309779), Ivana Pibiri (1309782), Marco Tutone (2654020), Riccardo Perriera (8473554)   +8 more
core   +1 more source

Nickel‐Catalyzed Three‐Component Difluoroalkylation‐Amination for the Direct Access to Anti‐Inflammatory β‐Difluoroalkyl Amines

Advanced Science, EarlyView.
A nickel‐catalyzed three‐component reductive fluoroalkylation‐amination strategy of N‐vinylamides for the direct access to the α‐amidyl‐β‐difluoroalkyl amines was reported here. The synthetic method features with broad substrate scope, mild conditions, high functional group tolerance, and convenience to handle.
Chang Xu, Fangting Ma, Fan Ding, Luyan Wang, Yunxi Li, Yunzhi He, Xingang Zhang, Siyu He, Dandan Liu   +8 more
wiley   +1 more source

Combinatorial targeting of G‐protein‐coupled bile acid receptor 1 and cysteinyl leukotriene receptor 1 reveals a mechanistic role for bile acids and leukotrienes in drug‐induced liver injury

Hepatology, EarlyView., 2022
CHIN117 is a dual cysteinyl leukotriene receptor 1 (CYSLTR1) antagonist and G‐protein‐coupled bile acid receptor 1 (GPBAR1) agonist. In the liver, GPBAR1 and CYSLTR1 are coexpressed by liver sinusoidal endothelial cells (LSECs), HSCs, circulating monocytes/macrophages, and liver resident macrophages (Kupffer cells).
Michele Biagioli, Silvia Marchianò, Cristina di Giorgio, Rosalinda Roselli, Martina Bordoni, Rachele Bellini, Bianca Fiorillo, Valentina Sepe, Bruno Catalanotti, Chiara Cassiano, Maria Chiara Monti, Eleonora Distrutti, Angela Zampella, Stefano Fiorucci   +13 more
wiley   +1 more source

A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand

Advanced Science, EarlyView.
Targeted protein degradation is often limited by the scarcity of usable E3 ligases. Herein, we report the first small‐molecule GPX4 degraders that incorporate either electrophilic warheads or a minimal azide group as an E3 recruitment ligand. The azide‐based degrader DK‐5070 effectively drives potent GPX4 degradation; mechanistic studies reveal that ...
Zehong Lin, Kang Duan, Rui Wan, Tao Jiang, Jinzhe Wei, Miao Sun, Mariia A. Skryl'nikova, Maxim A. Gureev, Zhi‐Min Zhang, Zhang Zhang, Ke Ding, Nan Ma, Tongzheng Liu, Yi Tan, Zhengqiu Li   +14 more
wiley   +1 more source

Site‐Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids

Angewandte Chemie, EarlyView.
Genetic code expansion (GCE) enables site‐specific installation of noncanonical amino acids containing bioorthogonal conjugation handles, allowing precise, homogeneous protein modification. This review examines the principles of orthogonal translation, surveys the chemistries available for chemoselective labeling, and highlights emerging multi‐site ...
Rahul Sarkar, Manas Joshi, Abhishek Chatterjee   +2 more
wiley   +2 more sources

A Site‐Aware Representation Learning Framework For Unified Molecular Interaction Modeling and Generative Design

Advanced Science, EarlyView.
MolDBG is a site‐aware, sequence‐only framework that unifies drug‐target affinity prediction, binding‐site identification, and affinity‐conditioned molecular generation for structured proteins. Guided by multi‐task binding‐site supervision, it aligns interaction‐critical residues before learning drug‐target representations and simultaneously infers ...
Gang Luo, Qianqian Zhang, Chenhao Wang, Zhiheng Yi, Alex Jinpeng Wang, Jing Tang, Min Li   +6 more
wiley   +1 more source

Beyond Nature's Blueprint: Macrocyclic Peptides Containing Unnatural Amino Acids in Therapeutic Development

Angewandte Chemie, EarlyView.
Strategic incorporation of unnatural amino acids transforms macrocyclic peptides into drug‐like molecules capable of engaging challenging targets. These building blocks enhance stability, permeability, and bioavailability, accelerating the development of next‐generation peptide therapeutics.
Krishna K. Sharma, Komal Sharma, Anku Sharma, Kamya Rao, Rahul Jain, Brett VanVeller   +5 more
wiley   +2 more sources

PharmacoForge: pharmacophore generation with diffusion models

Frontiers in Bioinformatics
Structure-based drug design (SBDD) is enhanced by machine learning (ML) to improve both virtual screening and de novo design. Despite advances in ML tools for both strategies, screening remains bounded by time and computational cost, while generative ...
Emma L. Flynn, Emma L. Flynn, Riya Shah , Ian Dunn , Ian Dunn , Rishal Aggarwal , Rishal Aggarwal , David Ryan Koes    +7 more
doaj   +1 more source

Dual Nickel/Photoredox‐Catalyzed Regio‐ and Enantioselective Alkenylation of Epoxides

Advanced Science, EarlyView.
Ni/photoredox‐catalyzed stereoconvergent cross‐electrophile coupling of racemic epoxides with alkenyl bromides is described, affording β‐alkenyl products with up to 95% ee, excellent E‐selectivity, and complete regiocontrol. These versatile intermediates enable diverse chiral synthons; mechanistic studies suggest a halide ring‐opening followed by ...
Hongyan Lan, Shengzhou Jin, Zhao‐Dong Xu, Guigen Li, Dingyi Wang   +4 more
wiley   +1 more source