Background Natural products have been an important source of lead compounds for drug discovery. How to find and evaluate bioactive natural products is critical to the achievement of drug/lead discovery from natural products. Methodology We collected 19,7201 natural products structures, reported biological activities and virtual screening results. Principal component analysis was employed to explore the chemical space, and we found that there was a large portion of overlap between natural products and FDA-approved drugs in the chemical space, which indicated that natural products had large quantity of potential lead compounds. We also explored the network properties of natural product-target networks and found that polypharmacology was greatly enriched to those compounds with large degree and high betweenness centrality. In order to make up for a lack of experimental data, high throughput virtual screening was employed. All natural products were docked to 332 target proteins of FDA-approved drugs. The most potential natural products for drug discovery and their indications were predicted based on a docking score-weighted prediction model. Conclusions Analysis of molecular descriptors, distribution in chemical space and biological activities of natural products was conducted in this article. Natural products have vast chemical diversity, good drug-like properties and can interact with multiple cellular target proteins.

Phosphoglycerate kinase 1 (PGK1), a critical component of the glycolytic pathway, relates to the development of various cancers. However, the mechanisms of PGK1 inhibition and physiological significance of PGK1 inhibitors in cancer cells are unclear. Long non-coding RNAs (lncRNA) play a vital role in tumor growth and progression. Here, we identified a lncRNA LINC00926 negatively correlated with PGK1 and predicting good clinical outcome of breast cancer. LINC00926 downregulates PGK1 expression by enhancing the ubiquitination of PGK1 mediated by E3 ligase STUB1. Moreover, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. FOXO3A/LINC00926/PGK1 axis regulates breast cancer glycolysis, tumor growth and lung metastasis both in vitro and in vivo. In breast cancer patients, LINC00926 expression is negatively correlated with PGK1 and positively correlated with FOXO3A expression. Our work established FOXO3A/LINC00926/PGK1 as a critical axis to regulate BC growth and progression. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.

To identify whether cartilage master regulator SRY-related protein 9 (SOX9) mediates A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) dysregulation during osteoarthritis (OA) cartilage degeneration. Twenty-two randomly selected OA patients were evaluated using Outerbridge Classification via arthroscopy. Haematoxylin-eosin (HE), Safranin O and Masson staining were performed for the histopathological assessment. The expression of ADAMTSs, collagen 2A1 (COL2A1), aggrecan (ACAN), cartilage oligomeric matrix protein (COMP) and SOX9 were examined using real-time quantitative Polymerase Chain Reaction (PCR) (RT-qPCR) and western blotting analysis. Immunohistochemistry (IHC) analysis was performed to investigate the production of ADAMTSs in cartilage tissues. The association between SOX9 production and ADAMTSs, COL2A1, ACAN, and COMP expression was established by full-depth cartilage biopsies. ADAMTSs expression levels were repressed at stage 1, while a significant increase was observed at the progressive stage of OA. SOX9 was upregulated at stage 1 and suppressed at a later stage of cartilage development, particularly in cartilage with severe damage. In addition, SOX9 repressed the expression of ADAMTSs and promoted COL2A1, ACAN and COMP expression in human chondrocytes. SOX9 was recruited to the promoters of ADAMTS-4 and ADAMTS-7. SOX9 expression was negatively correlated with ADAMTSs production and was positively associated with COL2A1, ACAN and COMP expression. Inhibition of ADAMTSs markedly increased the production of COL2A1, ACAN and COMP in chondrocytes isolated from the early stage of OA. These findings indicated that SOX9 upregulation might mediate ADAMTSs suppression at the early stage of human OA. In addition, SOX9 could be used as a potential therapeutic agent for human OA at an early stage.