The Keap1-Nrf2 pathway has been shown to be an important defense mechanism against oxidative stress, which may be an effective therapeutic strategy for many diseases. The research progresses on Keap1-Nrf2 pathway in inflammatory diseases were mainly reviewed. The basic components and activation mechanism of Keap1-Nrf2 pathway were introduced. The relationship between Keap1-Nrf2 pathway and the crosstalk between NF-κB pathway and HO-1 pathway, the expression of inflammatory mediators and enzymes, and inflammatory bodies were expounded. Natural product-derived inhibitors, small molecule inhibitors targeting Keap1-Nrf2 pathway and their clinical progress were introduced, and the potential application value of Keap1-Nrf2 pathway in the treatment of inflammation was discussed.

Sophora alopecuroides, a plant of the family Leguminosae, is one of the Daodi herbs in Ningxia. The active constituents of Sophora alopecuroides are abundant and complex, including alkaloids, flavonoids, volatile oils, steroids, polysaccharides, fatty acids and so on. In recent decades, a great number of domestic and overseas studies have been carried out on Sophora alopecuroides alkaloids, which have anti-hepatitis, anti-liver fibrosis, anti-cirrhosis, anti-liver failure and anti-liver cancer and other pharmacological effects. Clinically, Matrine-related drugs are used to treat hepatitis B virus infection and other diseases. This review aims to summarize the main active ingredients of Sophora alopecuroides, mainly focusing on the research progress in their treatment activities for liver diseases.

Objective To synthesize and investigate cytotoxicity of an indole-chalcone derivative FC58. Methods The target compound was synthesized through the Aldol condensation with 1-(3,4,5-trimethoxyphenyl)ethan-1-one and 1H-indole-3-carbaldehyde. The Cell Titer-Blue method was used to determine in vitro cytotoxicity. The cell cycle experiment was performed to analyze the action characteristics of FC58. Results FC58 exhibited high cytotoxicity against various leukemia cells and resulted in G2/M phase arrest. It showed stronger drug resistant index than traditional tubulin inhibitors such as paclitaxel, vinblastine and doxorubicin. Conclusion FC58 represents a promising lead compound for multi-drug resistant leukemia.

Receptor-interacting protein (RIP) kinase 1 is involved in immune-mediated inflammatory diseases including ulcerative colitis (UC) by regulating necroptosis and inflammation. Our group previously identified TAK-632 (

Coronavirus infection seriously threatens human health. There is no specific medication or vaccine so far. In recent years, domestic and foreign researchers have developed a variety of small-molecule inhibitors against the ligand S protein, RdRp, PL^pro and 3CL^pro of three highly pathogenic coronavirus, SARS-CoV，MERS-CoV，SARS-CoV-2. This article reviews the characteristics of these coronaviruses, action targets, small molecule inhibitors, and structure-activity relationships.

In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds and had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.

Human immunodeficiency virus (HIV) is the primary infectious agent of acquired immunodeficiency syndrome (AIDS), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the cornerstone of HIV treatment. In the last 20 years, our medicinal chemistry group has made great strides in developing several distinct novel NNRTIs, including 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), thio-dihydro-alkoxy-benzyl-oxopyrimidine (-DABO), diaryltriazine (DATA), diarylpyrimidine (DAPY) analogues, and their hybrid derivatives. Application of integrated modern medicinal strategies, including structure-based drug design, fragment-based optimization, scaffold/fragment hopping, molecular/fragment hybridization, and bioisosterism, led to the development of several highly potent analogues for further evaluations. In this paper, we review the development of NNRTIs in the last two decades using the above optimization strategies, including their structure-activity relationships, molecular modeling, and their binding modes with HIV-1 reverse transcriptase (RT). Future directions and perspectives on the design and associated challenges are also discussed.

Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus, the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.

Cancer stem cells play a crucial role in tumors'invasion, metastasis, recurrence and drug resistance.Investigation on the chemicals with tumor stem cell growth inhibitory activity has been greatly highlighted in the field of anti-tumor drug discovery.This paper briefly reviews the recent progress of chemical investigations on substances with tumor stem cell growth inhibitory activity , aiming to give readers a reference on anti-tumor drug discovery.

In 2015, more than 8 million people died from various kinds of cancers all over the world.Although traditional chemotherapeutic drugs are widely used in clinic, more than 50％ of cancers are significantly resistant to traditional chemotherapeutic drugs.Tubulin targeting agents have been confirmed to be effective anti-cancer drugs in clinic.However, some anti-microtubule agents developed resistance after long-term use, such as paclitaxel and vinblastine.In recent years, it is reported that tubulin modulators targeting on the colchicine-binding site are extremely effective against multi-drug resistant cancer cells.In this article, different anti-microtubule agents targeting multi-drug resistant cancers are reviewed.