F-CPI: A Multimodal Deep Learning Approach for Predicting Compound Bioactivity Changes Induced by Fluorine Substitution.

Fluorine (F) substitution is a common method of drug discovery and development. However, there are no accurate approaches available for predicting the bioactivity changes after F-substitution, as the effect of substitution on the interactions between compounds and proteins (CPI) remains a mystery. In this study, we constructed a data set with 111,168 pairs of fluorine-substituted and nonfluorine-substituted compounds.

Design, synthesis and biological evaluation of alginate oligosaccharide derivatives.

To discover new potential drug for acute kidney injury (AKI), a series of novel alginate oligosaccharide derivatives were synthesized and characterized by the spectroscopic analysis. By using the controlled experimental method, the target compounds were evaluated preliminarily for therapeutic activity in AKI. The results demonstrated that compounds 2a, 2b, 2c and 3b exhibited notable inhibitory activity against the expression of related proteins at 250 μg/ml in vitro.

Discovery of the potent covalent inhibitor with an acrylate warhead for SARS-CoV-2 3CL protease.

COVID-19 has caused severe consequences in terms of public health and economy worldwide since its outbreak in December 2019. SARS-CoV-2 3C-like protease (3CL), crucial for the viral replications, is an attractive target for the development of antiviral drugs. In this study, several kinds of Michael acceptor warheads were utilized to hunt for potent covalent inhibitors against 3CL.

Discovery of Novel 1-Phenylpiperidine Urea-Containing Derivatives Inhibiting β-Catenin/BCL9 Interaction and Exerting Antitumor Efficacy through the Activation of Antigen Presentation of cDC1 Cells.

Aberrant activation of the Wnt/β-catenin signaling is associated with tumor development, and blocking β-catenin/BCL9 is a novel strategy for oncogenic Wnt/β-catenin signaling. Herein, we presented two novel β-catenin variations and exposed conformational dynamics in several β-catenin crystal structures at the BCL9 binding site. Furthermore, we identified a class of novel urea-containing compounds targeting β-catenin/BCL9 interaction.

Effect of plasma exosome lncRNA on isoproterenol hydrochloride-induced cardiotoxicity in rats.

Isoprenaline hydrochloride (IH) is a β-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases.

Recombinant adeno-associated virus 8 vector in gene therapy: Opportunities and challenges.

In recent years, significant breakthroughs have been made in the field of gene therapy. Adeno-associated virus (AAV) is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of interest. Among the AAV vectors, AAV serotype 8 (AAV8) has attracted much attention for its efficient and stable gene transfection into specific tissues.

Design, synthesis and biological evaluation of peptidomimetic benzothiazolyl ketones as 3CL inhibitors against SARS-CoV-2.

A series of peptidomimetic compounds containing benzothiazolyl ketone and [2.2.1] azabicyclic ring was designed, synthesized and evaluated in the hope of obtaining potent oral 3CL inhibitors with improved pharmacokinetic properties.

Design, synthesis and biological evaluation of covalent peptidomimetic 3CL protease inhibitors containing nitrile moiety.

In this paper, a series of peptidomimetic SARS-CoV-2 3CL protease inhibitors with new P2 and P4 positions were synthesized and evaluated. Among these compounds, 1a and 2b exhibited obvious 3CL inhibitory activities with IC of 18.06 nM and 22.

Biodistribution of 89Zr-oxine-labeled human bone marrow-derived mesenchymal stem cells by micro-PET/computed tomography imaging in Sprague-Dawley rats.

Purpose: To develop a method for labeling human bone marrow mesenchymal stem cells (hMSCs) with 89Zr-oxine to characterize the biodistribution characteristics of hMSCs in normal Sprague-Dawley (SD) rats in real-time by micro-PET-computed tomography (micro-PET/CT) imaging.

Methods: 89Zr-oxine complex was synthesized from 89Zr-oxalate and 8-hydroxyquinoline (oxine). After hMSCs were labeled with the 89Zr-oxine complex, the radioactivity retention, viability, proliferation, apoptosis, differentiation, morphology, and phenotype of labeled cells were assessed.