Peng Zhan

Shandong University | SDU · Institute for Medicine Chemistry

In this manuscript, twenty‐one novel fluorinated piperazine‐hydroxyethylamine analogues were synthesized and tested against Plasmodium falciparum (Pf). Among tested compounds, two 13 g and 14 g exhibited promising inhibitory activity on Pf3D7 with IC50 values of 0.28 and 0.09 μM, respectively. Neither of the hits exhibited cytotoxicity on HepG2 cel...

T cell immunoglobulin and mucin domain–containing protein 3 (TIM-3) is an immune checkpoint that has critical roles in immune exhaustion. However, little is known about the mechanisms that regulate TIM-3 surface expression and turnover. Here, we report that human TIM-3 is palmitoylated by the palmitoyltransferase DHHC9 at residue cysteine 296 (Cys...

The continuous mutational nature of SARS-CoV-2 and its inter-species similarities emphasize the urgent need to design and develop more direct-acting antiviral agents against highly infectious variants. Herein, we report on...

This article presents the rapid identification of novel indolylarylsulfone (IAS) derivatives as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV-1 through a miniaturized click-chemistry-based combinatorial library approach.

The term cancer is used to describe a complex pathology characterized by the uncontrollable proliferation of cells, which displays a fast metastatic spread, being a disease with difficult treatment. In this context, Phosphatidylinositol 3-kinase (PI3K) represents a promising pathway to be inhibited, aiming to develop anticancer agents, since it per...

The COVID‐19 pandemic has required an expeditious advancement of innovative antiviral drugs. In this study, focused compound libraries are synthesized in 96‐ well plates utilizing modular click chemistry to rapidly discover potent inhibitors targeting the main protease (Mpro) of SARS‐CoV‐2. Subsequent direct biological screening identifies novel 1,...

Hyperuricemia is a condition when uric acid, a waste product of purine metabolism, accumulates in the blood. Untreated hyperuricemia can lead to crystal formation of monosodium urate in the joints, causing a painful inflammatory disease known as gout. These conditions are associated with many other diseases and affect a significant and increasing p...

BACKGROUND Despite endothelial dysfunction being an initial step in the development of hypertension and associated cardiovascular/renal injuries, effective therapeutic strategies to prevent endothelial dysfunction are still lacking. GPR183 (G protein-coupled receptor 183), a recently identified G protein-coupled receptor for oxysterols and hydroxyl...

In the current antiretroviral landscape, continuous efforts are still needed to search for novel chemotypes of human immunodeficiency virus type 1 (HIV‐1) inhibitors with improved drug resistance profiles and favorable drug‐like properties. Herein, we report the design, synthesis, biological characterization, and druggability evaluation of a class...

Multi-target drug treatment has become popular as a substitute for traditional monotherapy. Monotherapy can lead to resistance and side effects. Multi-target drug discovery is gaining importance as data on bioactivity becomes more abundant. The design of multi-target drugs is expected to be an important development in the pharmaceutical industry in...

Introduction: Hydrophobic tagging (HyT) technology presents a distinct therapeutic strategy diverging from conventional small molecule drugs, providing an innovative approach to drug design. This review aims to provide an overview of the HyT literature and future outlook to offer guidance for drug design. Areas covered: In this review, the autho...

The HIV capsid (CA) protein is a promising target for anti‐AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well‐documented CA inhibitor PF74 as our lead compound and designed a series of low‐molecular‐weight phenylalanine derivatives. Among them, compound 7t exhibited remarkable antiviral activity with a...

Non‐nucleoside reverse transcriptase inhibitors (NNRTIs) are an important component of anti‐acquired immunodeficiency syndrome treatment regimen. In the present work, with the previously reported compound K‐16c as lead, a series of novel 2,4,5‐trisubstituted pyrimidine derivatives were designed based on the cocrystal structure of K‐16c /RT, with th...

In this study, a novel series of diarylpyrimidine derivatives with Fsp ³ ‐enriched spirocycles were designed and synthesized to further explore the chemical space of the hydrophobic channel of the NNRTI‐binding pocket. The biological evaluation results showed that most of the compounds displayed effective inhibitory potency against the HIV‐1 wild‐t...

HIV-1 reverse transcriptase (RT) has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome (AIDS), but the inevitable drug resistance and side effects have always been major challenges faced by non-nucleoside reverse transcriptase inhibitors (NNRTIs). This work aimed to identify novel chemotypes of ant...

Abstract Background & Aims NK cells are enriched in liver and play critical roles in HCC. NK cell-based anti-HCC therapy is becoming attractive but still rare. Siglec-9 interacts with its ligand (Siglec-9L) and restrains NK cell functions, suggesting it is a potential therapeutic target. However, in situ Siglec-9/Siglec-9L interaction in HCC has no...

Recent groundbreaking advances in the structural biology of the glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) have provided critical insights into the molecular mechanisms underlying urate recognition and transport. Using cryo-electron microscopy (cryo-EM), researchers have elucidated the structures of these transporters at high res...

The N-methyl-d-aspartate (NMDA) receptors, which belong to the ionotropic Glutamate receptors, constitute a family of ligand-gated ion channels. Within the various subtypes of NMDA receptors, the GluN1/2A subtype plays a significant role in central nervous system (CNS) disorders. The present article aims to provide a comprehensive review of ligands...

Designing and developing new drugs is an expensive and time-consuming process, and there is a need to discover new tools or approaches that can optimize this process. Applied Computer-Aided Drug Design: Models and Methods compiles information about the main advances in computational tools for discovering new drugs in a simple and accessible languag...

Introduction: Selenium possesses numerous advantageous properties in the field of medicine, and a variety of selenium-containing compounds have been documented to exhibit anti-HIV activity. This paper aims to categorize these compounds and conduct SAR analysis to offer guidance for drug design and optimization. Areas covered: The authors present...

T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC′ cleft of Tim-3,...

Our previous studies have shown that the introduction of structurally diverse benzyl side chains at the C5-NH2 position of oseltamivir to occupy 150-cavity contributes to the binding affinity with neuraminidase and anti-influenza activity. To obtain broad-spectrum neuraminidase inhibitors, we designed and synthesised a series of novel oseltamivir d...

Seasonal and pandemic influenza virus infections not only pose a serious threat to human health but also cause tremendous economic losses and social burdens. However, due to the inherent high variability of influenza virus RNA genomes, the existing anti-influenza virus drugs have been frequently faced with the clinical issue of emerging drug-resist...

With our continuous endeavors in seeking potent anti-HIV-1 agents, we reported here the discovery, biological characterization, and druggability evaluation of a class of nonnucleoside reverse transcriptase inhibitors. To fully explore the chemical space of the NNRTI-binding pocket, novel series of dihydrothiopyrano [3,2-d]pyrimidines were developed...

Taking our previously reported HIV-1 NNRTIs BH-11c and XJ-10c as lead compounds, series of novel diarypyrimidine derivatives bearing six-membered non-aromatic heterocycles were designed to improve anti-resistance and drug-like profiles. According to the three rounds of in vitro antiviral activity screening, compound 12g was the most active inhibito...

Background: Acquired immunodeficiency syndrome (AIDS) has seriously endangered human life and health, the main pathogenic agent is human immunodeficiency virus type 1 (HIV-1). The combination antiretroviral therapy (cART) has shown serious drug resistance and side effects, and the discovery of HIV-1 capsid inhibitors is an effective way to solve th...

Interfering with the assembly of hepatitis B virus (HBV) capsid is a promising approach for treating chronic hepatitis B (CHB). In order to enhance the metabolic stability and reduce the strong hERG inhibitory effect of HBV capsid assembly modulator (CAM) GLS4, we rationally designed a series of carboxyl-containing heteroaryldihydropyrimidine (HAP)...

The SARS-CoV-2 3-chymotrypsin-like protease (3CL pro) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The N-substituted isatin derivative L-26 is a potential SARS-CoV-2 3CL pro inhibitor, but it has poor cell-based antiviral activity and high cytotoxicity. With L-26 as the lead compound, 58...

The Human Immunodeficiency Virus Type 1 (HIV-1) continues to be a major global health issue, with infection leading to Acquired Immunodeficiency Syndrome (AIDS). Despite advances in antiviral therapy, the need for new and more effective treatments remains critical. In this study, we determined the structure of the disulfide stabilised HIV-1 capsid...

Emerging drug design strategies in anti-influenza drug discovery, Acta Pharmaceutica Sinica B, https://doi. Running title Anti-influenza virus drug design strategies. J o u r n a l P r e-p r o o f This article reviews the application of emerging drug design strategies in the discovery of anti-influenza virus drugs, and lists the representative inhi...

Viral infections represent a major threat to human health and the global economy; however, most of the currently available antiviral drugs are not fully effective in restricting viral replication and selecting for drug-resistant variants. Targeted protein degradation technologies are promising strategies to avoid or delay the emergence of drug resi...

The main protease (Mpro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent Mpro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been...

Influenza viruses pose a significant threat to human health worldwide due to seasonal epidemics and occasional global pandemics. These viruses can cause severe upper respiratory tract infections that contribute to high morbidity and mortality rates. The emergence of drug-resistant influenza viruses has created the need for the development of novel...

To develop more potent HIV-1 inhibitors against a variety of NNRTIs-resistant strains, a series of 5-cyano substituted diarylpyridines was designed based on the cocrystal structural analysis. Among them, I-5b showed the greatest potency (EC50 = 5.62-171 nM) against the wild-type (WT) and mutant HIV-1 strains. Especially for K103 N, I-5b exhibited o...

HIV-1 capsid (CA) is an attractive target for its indispensable roles in the viral life cycle. We report the design, synthesis, and mechanistic study of a novel series of 2-piperazineone peptidomimetics as HIV capsid modulators by mimicking the structure of host factors binding to CA. F-Id-3o was the most potent compound from the synthesized series...

STING (stimulator of interferon genes) exerts protective cellular responses to viral infection via induction of interferon production and autophagy. Here, we report the role of STING in modulating the immune responses toward fungal infection. Upon Candida albicans stimulation, STING transited alongside the endoplasmic reticulum (ER) to the phagosom...

In the current landscape of antiretroviral options, there remains an urgent need for novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) with improved resistance profiles and safety properties. Herein, a series of novel tetrahydropyrido[4,3-d]pyrimidine derivatives were discovered utilizing the "escape from flatland" strategy. The most p...

Hepatitis B virus (HBV) infection is a major global health problem that puts people at high risk of death from cirrhosis and liver cancer. The presence of covalently closed circular DNA (cccDNA) in infected cells is considered to be the main obstacle to curing chronic hepatitis B. At present, the cccDNA cannot be completely eliminated by standard t...

HIV-1 reverse transcriptase is one of the most attractive targets for the treatment of AIDS. However, the rapid emergence of drug-resistant strains and unsatisfactory drug-like properties seriously limit the clinical application of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Here we show that a series of piperazine sulfonyl-bear...