Publications by authors named "Minghai Tang"

Article Synopsis
  • - The Chinese government enacted legislation in 2021 to enhance the role of pharmacists in healthcare, aiming to improve the accessibility and rational use of pharmaceutical services in medical institutions.
  • - A time-series study analyzed pharmacist resource supply and demand across 31 regions in China from 2016 to 2020, utilizing data from the National Health Commission to evaluate resource allocation equity through health resource density, Gini coefficients, and Theil indexes.
  • - Findings showed a higher annual growth rate for healthcare staff (5.67%) compared to pharmacists (3.03%), with significant disparities in geographic versus population distribution of pharmacist resources, indicating challenges in equitable access across regions.
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Chronic kidney disease (CKD) is a condition characterized by functional deterioration with sustained inflammation and progressive fibrosis of the kidneys affecting over 800 million people worldwide. The P2X7 receptor (P2X7R) plays a key role in CKD progression. Our previous P2X7R antagonists demonstrated good efficacy for treating kidney injury but were limited by low oral exposure and short half-life, restricting their application.

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Chlorfenapyr is a novel broad-spectrum insecticide derived from natural pyrrole derivatives produced by Streptomyces spp. It acts as a pro-insecticide and is metabolically converted to the active metabolite, tralopyril. Chlorfenapyr poisoning is known for its delayed neurological symptoms and high mortality.

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The NLRP3 inflammasome is a multiprotein complex that is a component of the innate immune system, involved in the production of pro-inflammatory cytokines. Its abnormal activation is associated with many inflammatory diseases. In this study, we designed and synthesized a series of NLRP3 inflammasome inhibitors based on pyridazine scaffolds.

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Herein, we described the rational drug design and synthesis of a series of 5-amino-4-fluoro-1-benzo[]imidazole-6-carboxamide derivatives that inhibit MEK and RAF kinases. The detailed screening cascades revealed that was a preferred compound, which might act like a "clamp" to stabilize the MEK/RAF complex, thereby effectively inhibiting MEK1, BRAF, and BRAF with IC values of 28, 3, and 3 nM, respectively. possessed an excellent selectivity over other 312 human-related kinases at 1 μM.

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Erianin, a natural compound derived from Dendrobium, has shown significant anticancer properties against a wide range of cancer cells. Despite the identification of multiple mechanisms of action for erianin, none of these mechanisms fully account for its broad-spectrum effect. In this study, we aimed to identify the cellular target and underlying mechanism responsible for the broad-spectrum antitumor effects of erianin.

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Article Synopsis
  • Janus Kinase 3 (JAK3) plays a key role in immune cell signaling and is a potential treatment target for rheumatoid arthritis (RA).
  • Researchers developed new JAK3 inhibitors, J1b and J1f, with improved potency, and found that compound 9a showed the strongest effectiveness and low toxicity in tests.
  • Compound 9a selectively inhibits JAK3, minimizing effects on other kinases, and demonstrated the ability to reduce inflammation and lymphocyte proliferation, indicating its promise for RA treatment.
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Background: Anaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic strategies to curb its progression and improve patient prognosis. Halofuginone (HF), a derivative of febrifugine, has displayed antitumor properties across various cancer types. However, there is a paucity of published research focused on the potential of HF to enhance the clinical efficacy of treating ATC.

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The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized.

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Selective inhibition of Janus kinase 3 (JAK3) is a promising strategy for the treatment of autoimmune diseases. Based on the discovery of a hydrophobic pocket unutilized between the lead compound RB1 and the JAK3 protein, a series of covalent JAK3 inhibitors were prepared by introducing various aromatic fragments to RB1. Among them, J1b (JAK3 IC = 7.

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Our previous studies have demonstrated that BML284 is a colchicine-site tubulin degradation agent. To improve its antiproliferative properties, 45 derivatives or analogs of BML284 were designed and synthesized based on the cocrystal structure of BML284 and tubulin. Among them, 5i was the most potent derivative, with IC values ranging from 0.

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Traf2-and Nck-interacting protein kinase (TNIK) plays an important role in regulating signal transduction of the Wnt/β-catenin pathway and is considered an important target for the treatment of colorectal cancer. Inhibiting TNIK has potential to block abnormal Wnt/β-catenin signal transduction caused by colorectal cancer mutations. We discovered a series of 6-(1-methyl-1H-imidazole-5-yl) quinoline derivatives as TNIK inhibitors through Deep Fragment Growth and virtual screening.

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Gasdermin D (GSDMD) serves as a vital mediator of inflammasome-driven pyroptosis. In our study, we have identified NU6300 as a specific GSDMD inhibitor that covalently interacts with cysteine-191 of GSDMD, effectively blocking its cleavage while not affecting earlier steps such as ASC oligomerization and caspase-1 processing in AIM2- and NLRC4-mediated inflammation. On the contrary, NU6300 robustly inhibits these earlier steps in NLRP3 inflammasome, confirming a unique feedback inhibition effect in the NLRP3-GSDMD pathway upon GSDMD targeting.

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Article Synopsis
  • - Flonoltinib Maleate (FM) is a targeted medication in phase I/IIa trials in China for myeloproliferative neoplasms, selectively inhibiting JAK2/FLT3. - Researchers used C-labeled FM to study its distribution, metabolism, and excretion in rats, finding FM had widespread distribution and rapid clearance without organ toxicity risks. - The study identified 17 metabolites and proposed a metabolic pathway for FM, revealing that most of the drug is excreted through bile and feces, while less than 10% is eliminated through urine.
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Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important regulatory factor in the necroptosis signaling pathway, and is considered an attractive therapeutic target for treating multiple inflammatory diseases. Herein, we describe the design, synthesis, and structure-activity relationships of 4-amino-1,6-dihydro-7H-pyrrolo [2,3-d]pyridazin-7-one derivatives as RIPK1 inhibitors. Among them, 13c showed favorable RIPK1 kinase inhibition activity with an IC value of 59.

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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with an insidious onset and poor prognosis. Pomegranate is a fruit rich in many natural products with anti-cancer potential; however, its direct biological effects are difficult to evaluate in vitro because of changes in its active components after absorption and metabolism. This study was conducted to prepare pomegranate juice-containing serum (PJ serum) by gavage of pomegranate juice (PJ) in rats and to collect serum.

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Given the multifaceted biological functions of DNA-PK encompassing DNA repair pathways and beyond, coupled with the susceptibility of DNA-PK-deficient cells to DNA-damaging agents, significant strides have been made in the pursuit of clinical potential for DNA-PK inhibitors as synergistic adjuncts to chemo- or radiotherapy. Nevertheless, although substantial progress has been made with the discovery of potent inhibitors of DNA-PK, the clinical trial landscape requires even more potent and selective molecules. This necessitates further endeavors to expand the repertoire of clinically accessible DNA-PK inhibitors for the ultimate benefit of patients.

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Cytoplasmic vacuolation-associated cell death, known as methuosis, offers a promising nonapoptotic approach for cancer treatment. In this study, we outline the synthesis and evaluation of potent methuosis-inducing compounds. These compounds selectively induce cell death, characterized by extensive cytoplasmic vacuolation in HeLa and MDA-MB-231 cells.

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Article Synopsis
  • * Recent research has focused on developing small-molecule inhibitors that target the NLRP3 inflammasome as a potential anti-inflammatory treatment.
  • * This text provides an overview of current clinical trials and the chemical structures of these inhibitors to support future drug development aimed at treating diseases linked to NLRP3 inflammasome dysregulation.
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Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract with the second highest mortality rate globally. is a widely used traditional medicinal plant, exhibiting antitumor activity against various tumor cells. At present, research on the effect of on CRC is limited to in vitro cytotoxicity, lacking comprehensive mechanism investigations.

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NLRP3 is an intracellular sensor protein that causes inflammasome formation and pyroptosis in response to a wide range of stimuli. Aberrant activation of NLRP3 inflammasome has been implicated in various chronic inflammatory diseases, making it a promising target for therapeutic intervention. In this work, a series of novel triazinone inhibitors of NLRP3 inflammasome were designed and synthesized.

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Sepsis-associated acute kidney injury (AKI) is a serious clinical problem, without effective drugs. Abnormal activation of the purinergic P2X7 receptor (P2X7R) in septic kidneys makes its antagonist a promising therapeutic approach. Herein, a series of novel P2X7R antagonists were designed, synthesized, and structurally optimized.

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ATM plays an important role in DNA damage response and is considered a potential target in cancer therapies. In this study, a goal-directed molecular generation approach based on ligand similarity and target specificity was applied to sample active molecules, and they were screened virtually to identify the theoretical lead compound , which was later shown to inhibit ATM adequately. However, there is a main concern about its poor metabolic stability .

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Salt-inducible kinases (SIKs) play a crucial role in inflammation process, acting as molecular switches that regulate the transformation of M1/M2 macrophages. HG-9-91-01 is a SIKs inhibitor with potent inhibitory activity against SIKs in the nanomolar range. However, its poor drug-like properties, including a rapid elimination rate, low in vivo exposure and high plasma protein binding rate, have hindered further research and clinical application.

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