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Article
143D, a novel selective KRASG12C inhibitor exhibits potent antitumor activity in preclinical models
The KRASG12C mutant has emerged as an important therapeutic target in recent years. Covalent inhibitors have shown promising antitumor activity against KRASG12C-mutant cancers in the clinic. In this study, a stru...
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Article
Discovery and characterization of a novel cGAS covalent inhibitor for the treatment of inflammatory bowel disease
Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, acts as a nucleotidyl transferase that catalyzes ATP and GTP to form cyclic GMP-AMP (cGAMP) and plays a critical role in innate immunity. Hyperactivation...
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Article
Discovery and identification of a novel small molecule BCL-2 inhibitor that binds to the BH4 domain
The B-cell lymphoma 2 (BCL-2) protein family plays a pivotal role in regulating the apoptosis process. BCL-2, as an antiapoptotic protein in this family, mediates apoptosis resistance and is an ideal target fo...
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Article
AlphaFold2 versus experimental structures: evaluation on G protein-coupled receptors
As important drug targets, G protein-coupled receptors (GPCRs) play pivotal roles in a wide range of physiological processes. Extensive efforts of structural biology have been made on the study of GPCRs. Howev...
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Article
Open AccessSafety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects
VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple a...
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Article
Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein
An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human...
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Article
A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors
The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly pot...
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Article
P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib
Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved...
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Article
Natural product 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose is a reversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase
Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate deh...
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Article
Crystallography-guided discovery of carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators: insights into different protein behaviors with “short” and “long” inverse agonists
A series of 6-substituted carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators were discovered through 6-position modification guided by insights from the crystallographic profiles ...
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Article
Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients
Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved prot...
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Article
The inhibitory mechanism of aurintricarboxylic acid targeting serine/threonine phosphatase Stp1 in Staphylococcus aureus: insights from molecular dynamics simulations
Serine/threonine phosphatase (Stp1) is a member of the bacterial Mg2+- or Mn2+- dependent protein phosphatase/protein phosphatase 2C family, which is involved in the regulation of Staphylococcus aureus virulence....
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Article
Identification of small molecule inhibitors targeting the SMARCA2 bromodomain from a high-throughput screening assay
SMARCA2 is a critical catalytic subunit of the switch/sucrose non-fermenting (SWI/SNF) chromatin remodeling complexes. Dysregulation of SMARCA2 is associated with several diseases, including some cancers. SMAR...
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Article
Open AccessThe HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1
Our previous study has demonstrated that hepatocyte nuclear factor 1α (HNF1α) exerts potent therapeutic effects on hepatocellular carcinoma (HCC). However, the molecular mechanisms by which HNF1α reverses HCC ...
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Article
Development of a high-throughput fluorescence polarization assay for the discovery of EZH2-EED interaction inhibitors
Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. The interaction of EZH2 with embryonic ectoderm development (EED) is required for EZH2's catalytic acti...
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Article
Conformation and dynamics of the C-terminal region in human phosphoglycerate mutase 1
Phosphoglycerate mutase 1 (PGAM1), an important enzyme in glycolysis, is overexpressed in a number of human cancers, thus has been proposed as a promising metabolic target for cancer treatments. The C-terminal...
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Article
High yield and efficient expression and purification of the human 5-HT3A receptor
To establish a method for efficient expression and purification of the human serotonin type 3A receptor (5-HT3A) that is suitable for structural studies.
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Article
Novel Bayesian classification models for predicting compounds blocking hERG potassium channels
A large number of drug-induced long QT syndromes are ascribed to blockage of hERG potassium channels. The aim of this study was to construct novel computational models to predict compounds blocking hERG channels.
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Article
Binding sensitivity of adefovir to the polymerase from different genotypes of HBV: molecular modeling, docking and dynamics simulation studies
To investigate the molecular mechanisms underlying the influence of DNA polymerase from different genotypes of hepatitis B virus (HBV) on the binding affinity of adefovir (ADV).
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Article
Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels
This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels.
