Minyong LiShandong University | SDU · School of Pharmaceutical Sciences
Minyong Li
Doctor of Philosophy
About
274
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Introduction
Additional affiliations
April 2009 - January 2022
November 2007 - April 2009
September 2005 - October 2007
Education
September 2000 - June 2005
September 1995 - July 1999
Publications
Publications (274)
Proteolysis targeting chimeras (PROTACs) are dual-functional hybrid molecules that can selectively recruit an E3 ubiquitin ligase to a target protein to direct the protein into the ubiquitin-proteasome system (UPS), thereby selectively reducing the target protein level by the ubiquitin-proteasome pathway. Nowadays, small-molecule PROTACs are gainin...
The Ca2+ release-activated Ca2+ (CRAC) channels control many Ca2+-modulated physiological processes in mammals. Hyperactivating CRAC channels are known to cause Stormorken syndrome. Here we show the design of azopyrazole-derived photoswitchable CRAC channel inhibitors (designated piCRACs), which enable optical inhibition of store-operated Ca2+ infl...
Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compo...
By fusing several environment-sensitive fluorophores to the pharmacophore mirabegron, a series of new fluorescent ligands for β-adrenergic receptors (β-ARs) were produced with a turn-on mechanism and high binding affinity to β-ARs efficiently. Compound L5 with the pyridinium moiety possessed the most favorable combination of properties after system...
Carboxylesterase (CES), a main hydrolysis enzyme family in human body, plays a crucial role in drug metabolism. Among them, CES1 and CES2 are the primary subtypes, and each exhibits distinct...
Targeted protein degradation (TPD) strategies, such as proteolysis-targeting chimeras (PROTACs) only work for intracellular protein degradation because they involve the intracellular protein degradation machinery. Several new technologies have emerged in recent years for TPD of extracellular and membrane proteins. Even though some progress has been...
For the precise visualization of GPCR, subtype selectivity of turn-on fluorescent ligands is of major relevance. Although there are many thriving β-adrenergic receptors (β-ARs) probes, none of them are selective to the β3-subtype, which severely limits the development of β3-AR investigations. Using a polyethylene glycol (PEG) chain to conjugate the...
Targeted protein degradation (TPD) strategies open up new avenues for therapeutics and provide powerful tools for biological inquiry. Herein, we present a brand-new approach, termed heat shock protein 90 (HSP90)-mediated targeting chimeras (HEMTACs), to induce intracellular protein degradation by bridging a target protein to HSP90 to drive the down...
Nicotinamide phosphoribosyl transferase (NAMPT) has been regarded as an attractive target for cancer therapy. However, there is a lack of chemical tools for real-time visualization and detection of NAMPT. Herein, the first fluorescent and theranostic probes were designed for imaging NAMPT, which had dual functions of diagnosis and treatment. The de...
The cost of antitumor drug development is enormous, yet the clinical outcomes are less than satisfactory. Therefore, it is of great importance to develop effective drug screening methods that enable accurate, rapid, and high‐throughput discovery of lead compounds in the process of preclinical antitumor drug research. An effective solution is to use...
Smart conversion of supramolecular structures in vivo is an attractive strategy in cancer nanomedicine, which is usually achieved via specific peptide sequences. Here we developed a lysosomal targeting small‐molecule conjugate, PBC, which self‐assembles into nanoparticles at physiological pH and smartly converts to nanofibrils in lysosomes of tumor...
Smart conversion of supramolecular structures in vivo is an attractive strategy in cancer nanomedicine, which is usually achieved via specific peptide sequences. Here we developed a lysosomal targeting small‐molecule conjugate, PBC, which self‐assembles into nanoparticles at physiological pH and smartly converts to nanofibrils in lysosomes of tumor...
Bioluminescence (BL), the emission light resulting from the enzyme-catalyzed oxidative reaction, is a powerful imaging modality for monitoring biological phenomena both in vitro and in vivo. Coelenterazine (CTZ), the known widespread luciferin found in bioluminescent organisms, develops bioluminescence imaging (BLI). Here, we describe an approach t...
The firefly luciferase system is the most extensively utilized bioluminescence system in the field of life science at the moment. In this work, we designed and synthesized a series of alkene-conjugated luciferins to develop new firefly bioluminescence substrates, and further evaluated their activities in vitro and in vivo. It is worth noting that t...
Enantioselective, intermolecular alkene arylamination has been achieved through gold redox catalysis. Screening of ligands revealed chiral P,N ligands as the optimal choice, giving alkene aminoarylation with good yields (up to 80 %) and excellent stereoselectivity (up to 99 : 1 er). As the first example of enantioselective gold redox catalysis, thi...
Head and neck squamous cell carcinoma (HNSCC) is a lethal disease with a terrible prognosis, accounting for more than 900,000 new cases and 500,000 deaths each year, nevertheless, its pharmacotherapy is rather limited. Parbendazole was previously identified as a potential HNSCC therapy candidate in our research. Herein, we report the discovery of t...
Enantioselective gold redox catalysis was achieved with newly designed chiral hemilabile P,N ligands (shown as a heavy load in the truck). We reveal a new strategy through a two‐step sequence: A) Apply a chiral hemilabile P,N ligand at the AuI stage to promote AuI oxidative addition toward aryl iodide; B) nucleophilic addition to a chiral AuIII int...
As a neurotransmitter, norepinephrine (NE) is critical for psychiatric conditions, neurodegenerative diseases, and pheochromocytoma. A real-time and noninvasive method for the detection of NE as a tracer to investigate the NE-relevant disease treatment process is urgently desirable. Herein, we successfully developed a turn-on NE bioluminescent prob...
A novel TrxR inhibitor Au-24 and its inhibitory ability to hepatocellular carcinoma in vitro and in vivo is reported herein. Au-24 can suppress HepG2 cells from proliferating by lowering mitochondrial membrane potential (MMP) and increasing reactive oxygen species (ROS) levels, resulting in oxidative stress, which causes DNA damage, autophagy, cell...
As a critical member of G protein-coupled receptors (GPCRs), G protein-coupled receptor 120 (GPR120) is a potential target for many physiological diseases, such as type 2 diabetes mellitus, inflammation, and obesity. Considering that small-molecule fluorescent ligands can combine the advantages of visualization, high sensitivity and selectivity, we...
The main effect of Vanin-1/VNN1 is related to its pantetheinase sulfhydrylase activity, which can hydrolyze pantetheine into pantothenic acid and cysteamine. In recent studies, the enzymatic activity of vanin-1/VNN1 has been found to be essential in the development of many diseases. The study of specific vanin-1/VNN1 inhibitors can give us a deeper...
Bioluminescence imaging (BLI) is a widely applied visual approach for real-time detecting many physiological and pathological processes in a variety of biological systems. Based on the caging strategy, lots of bioluminescent probes have been well developed. While the targets react with recognizable groups, caged luciferins liberate luciferase subst...
C-mesenchymal-epithelia transition factor (c-Met) is highly expressed in various solid tumors such as gastric cancer, liver cancer, and lung cancer, playing a pivotal role in the growth, maintenance, and development of different tumor cells. In this study, three small-molecule fluorescent probes (5, 11, 16) targeting c-Met were developed, and their...
The anticancer therapy strategy mediated by tumor-targeting bacteria needs better visualization tools for imaging and monitoring bacteria in vivo. The probiotic strain Escherichia coli Nissle 1917 (EcN), one of the tumor-targeting bacteria, leads to the potential application for cancer therapy. Here, we report the development and application of a l...
The outbreak of severe pneumonia at the end of 2019 was proved to be caused by the SARS-CoV-2 virus spreading out the world. And COVID-19 spread rapidly through a terrible transmission way by human-to-human, which led to many suspected cases waiting to be diagnosed and huge daily samples needed to be tested by an effective and rapid detection metho...
In recent years, various methods for detecting exogenous and endogenous hypochlorite have been studied, considering its essential role as a biomolecule. However, the existing technologies still pose obstacles such as their invasiveness, high costs, and complicated operation. In the current study, we developed a glow-type chemiluminescent probe, HCC...
Nanoluciferase (NLuc) is the emerging commercially available luciferase considering its small size and superior bioluminescence performance. Nevertheless, this bioluminescence system has some limitations, including narrow emission wavelength and single substrate. Herein, a series of novel furimazine derivatives at the C-6 and C-8 positions of the i...
Local polarity can affect the physical or chemical behaviors of surrounding molecules, especially in organisms. Cell polarity is the ultimate feedback of cellular status and regulation mechanisms. Hence, the abnormal alteration of polarity in organisms is closely linked with functional disorders and many diseases. It is incredibly significant to mo...
The catalytic properties of small-molecule proteolysis targeting chimeras (PROTACs) may lead to uncontrolled degradation. Therefore, the main disadvantages of PROTACs are non-cancer specificity and relatively high toxicity, which limit the clinical application of PROTACs. The photocontrolled PROTACs (photoPROTACs) were proposed to overcome this iss...
Fluorescent ligands have emerged as powerful tools for noninvasive research of G protein-coupled receptors (GPCRs), since they could provide the invaluable information regarding GPCRs’ structure and function in vitro. However, the in vivo applications of thus tools are hampered owing to their short-wavelength spectra and lack of fluorogenic switch....
Hydrogen sulfide (H2S), the third gaseous transmitter after CO and NO, is a double-edged sword in the human body. A specific concentration of H2S can attenuate myocardial ischemia-reperfusion injury by preserving mitochondrial function, in contrast, cause illness, including inflammation and stroke. There are already some probes for the real-time mo...
The novel fluorescent agonists were discovered herein for α1-adrenergic receptors (α1-ARs) based on photoinduced electron transfer (PeT) off-on switch by conjugating the fluorophore 7-(diethylamino)coumarin-3-carboxylic acid with phenylephrine. After careful evaluation, these probes exhibited efficient binding affinity with α1-ARs and could be appl...
Pyroglutamate aminopeptidase (PGP) specifically cleaves the peptide bond of pyroglutamic acid linked to the N-terminal end of a polypeptide or protein. Previous studies showed that PGP was associated with several physiological processes and diseases especially those involving inflammation. Utilizing a ‘caging’ strategy, we designed and synthesized...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22419-2
Artificial sweeteners (ASs) have generally been applied as food additives to improve the taste of sweetness. Thus, their potential toxic effects have received extensive attention. Saccharin (SAC), discovered more than a century ago, has been used as the first noncaloric AS in foods and beverages for over 100 years. Although the toxicological effect...
Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropi...
Small-molecule fluorescent probes are powerful tools in chemical analysis and biological imaging. However, as the foundation of probe design, the meager existing set of core fluorophores have largely limited the diversity of current probes. Consequently, there is a high demand to discover fluorophores with new scaffolds and optimize the existing fl...
Ca2+-regulated photoproteins responsible for bioluminescence of a variety of marine organisms are single-chain globular proteins within the inner cavity of which the oxygenated coelenterazine, 2-hydroperoxycoelenterazine, is tightly bound. Alongside with native coelenterazine, photoproteins can also use its synthetic analogues as substrates to prod...
The first small molecule fluorescent turn-on probes for detecting PDEδ protein were rationally designed, which showed reasonable fluo-rescent properties and can be applied into visualizing the PDEδ protein at the living cell and tissue levels. The qPCR results showed that the mRNA expression of KRAS, PDEδ, AKT1, MAPK1, MEK7, RAF1 and mTOR were down...
Sulfites are widely used as preservative and antioxidant additives in food and drug. A non-invasive method for in vivo imaging of sulfite represents a powerful tool for estimating its potential effects in living organisms. Herein, we report the design, development, and application of sulfite bioluminescent probes (SBPs) for the analyte-specific det...
NanoLuc (NLuc)-furimazine bioluminescence system offers several advantages over established systems, including improved stability, smaller size, and >150-fold enhancement in bioluminescence. Herein, we designed and synthesized a series of bioluminescent substrates with varying at the C-6 position of furimazine for NLuc-furimazine bioluminescence sy...
Histone deacetylases (HDACs) are proteases that can catalyze the deacetylation of histones to inhibit gene transcription. Since mutations and/or aberrant expression of various HDACs are frequently associated with human diseases, particularly cancers, HDACs are important therapeutic targets for many human tumors. However, there are still relatively...
Cysteine (Cys) is a semi-essential amino acid that exerts a vital role in numerous biological functions. A noninvasive method for in vivo imaging of cysteine could represent a valuable tool for research cysteine and its complex contributions in living organisms. Thus, we developed a turn-on bioluminescence probe (CBP) not only for detecting exogeno...
Based on the structural optimization work, probe 9-11 with practical activity and selectivity in tissue as well as living cell lines are well de-signed and synthesized. All the probes showed potent inhibitory and acceptable cell toxicity compared with commercially available p53-MDM2 inhibitor Nutlin-3, and can increase the protein expression level...
Bioluminescent imaging (BLI) technology has been extensively applied due to various advantages such as noninvasiveness, high sensitivity and selectivity, excellent biocompatibility and real-time visualization and monitoring. The firefly luciferase (Fluc)/luciferin system, one of the principal bioluminescent systems, has been developed as a sensor f...
Selenocysteine (Sec), a vital member of reactive selenium species, is closely implicated in diverse pathophysiological states, including cancer, cardiovascular disease, diabetes, neurodegenerative diseases, and male infertility. Monitoring Sec in vivo is of significant interest for understanding the physiological roles of Sec and the mechanisms of...
GPR120 is a novel target for the treatment of metabolic disease and type 2 diabetes. The small-molecule fluorescent probe could help us locate GPR120 visually and guide in-depth study of GPR120. In this study, we synthesized six nonacidic sulfonamide fluorescent probes and tested their optical and biological properties. Compared to previous probes...
Recently, artificial sweeteners have received widespread attention as the emerging environmental pollutants, among which, acesulfame (ACE) is ubiquitously present and extremely persistent in the ecosystem. Although the environmental behavior of ACE has already been well studied, its chronic eco-toxicological effects on aquatic organisms are rarely...
Fibroblast activation protein-α (FAP), as a crucial member of cell surface glycoprotein, highly expresses in reactive fibroblasts of tumors and several fibrosis diseases. It is a potential target for drug design and also reported as a prodrug strategy to increase the therapeutic window of some anticancer agents. In this work, we developed the first...
A series of novel fluorescent agonists (5a-c) were well developed herein with turn-on switch for α1-adrenergic receptors (α1-ARs) by con-jugating the environment-sensitive fluorophore, 4-chloro-7-nitrobenzoxadiazole, with phenylephrine. Overall, these probes exhibited efficient binding and apparent fluorescence intensity changes (up to 10-fold) upo...
Iron plays an essential role in biological system. An approach for in vivo imaging of this metal ion is needed to investigate its complex contributions to physiological and pathological processes. Herein, we present a bioluminescent probe FP-1 as a powerful tool for targeting Fe ²⁺ detection in vitro and in vivo. The turn-on sensing scheme is based...
Glioblastoma (GBM) is among the most common and malignant types of primary brain tumors in adults, with a dismal prognosis. Although alkylating agents such as temozolomide are widely applied as the first-line treatment for GBM, they often cause chemoresistance and remain ineffective with recurrent GBM. Alternative therapeutics against GBM are urgen...
Based on the scaffold of astemizole, three novel turn-on fluorescent probes (N1-N3) for Human Ether-a-go-go-Related Gene (hERG) potassium channel were developed herein. These probes have reasonable fluorescent properties, acceptable cell...
Based on the scaffold of astemizole and E-4031, four AIE light-up probes (L1–L4) for Human Ether-a-go-go-Related Gene (hERG) potassium channel were developed herein using AIE fluorogen(TPE). These probes showing advantages such as low background interference, superior photostability, acceptable cell toxicity, and potent inhibitory activity, which c...
Tyrosinase, a copper-containing enzyme, existing widely in plants, animals and microorganisms, usually is served as an important biomarker in melanoma, and also related to the hyperpigmentation of the skin, melasma, age spots and albinism. At present, only one bioluminescent probe was applied to image tyrosinase in cells. Thus, it’s of great signif...
To develop a strategy for visualizing palladium species in the biological system, several turn-on bioluminescent probes were designed and synthesized by using a Pd-induced reductive reaction herein. Such probes exhibited high sensitivity (detection limit: 0.5 μM) and excellent selectivity toward Pd²⁺ in vitro. In particular, probe 2 was identified...
Pantetheinase, a glycosylphosphatidylinositol (GPI) anchored enzyme, overexpresses in intestine, liver and kidney with various biological functions such as its linkage to the inflammation and some metabolic diseases. It can hydrolysis pantetheine to cysteamine, an antioxidant, and pantothenic acid (Vitamin B5) that is an essential component of coen...
The calcium release‐activated calcium (CRAC) channel, composed of ORAI and stromal interaction molecules (STIM), represents a prototypical example of store‐operated calcium entry in mammals. The ORAI‐STIM signaling occurs at membrane contact sites formed by close appositions between the endoplasmic reticulum (ER) and the plasma membrane. ORAI1 is a...
To develop a photoactivatable bioluminescence imaging technique, a set of high and efficient photoactivatable substrates for Renilla luciferase has been well designed and synthesized. Surprisingly, all of them could release...
A set of high and efficient caged luciferin derivatives exhibited low cytotoxicity and prolonged bioluminescence in vitro and in vivo .
Spannungsgesteuerte Calciumkanäle (VGCCs) sind wichtig für Therapiemethoden in Gefäßheilkunde und Neuropsychiatrie. In ihrer Zuschrift (DOI: 10.1002/ange.201713080) stellen Y. Zhou, Y. Wang et al. neuartige, genetisch kodierte und photoschaltbare Inhibitoren für VGCCs vor, die Ca2+‐Signale und biologische Aktivitäten von anregbaren Zellen beeinflus...
Voltage‐gated calcium channels (VGCCs) are important therapeutic targets for cardiovascular and neuropsychiatric disorders. In their Communication (DOI: 10.1002/anie.201713080), Y. Zhou, Y. Wang et al. report the engineering of a novel class of genetically encoded photoswitchable inhibitors of VGCCs to control Ca2+ signals and biological activity i...
As a trace element nutrient, cobalt is critical for both prokaryotes and eukaryotes. In the current study, a turn-on Cobalt Bioluminescent Probe 1 (CBP-1) for the detection of cobalt has been successfully developed based on oxidative C-O bond cleavage. This probe exhibited high selectivity and sensitivity towards cobalt over other analytes. By usin...
Voltage‐gated Ca2+ (CaV) channels mediate Ca2+ entry into excitable cells to regulate a myriad of cellular events following membrane depolarization. Here, we report the engineering of RGK GTPases, a class of genetically encoded CaV channel modulators, to enable photo‐tunable modulation of CaV channel activity in excitable mammalian cells. This opto...
Voltage‐gated Ca2+ (CaV) channels mediate Ca2+ entry into excitable cells to regulate a myriad of cellular events following membrane depolarization. Here, we report the engineering of RGK GTPases, a class of genetically encoded CaV channel modulators, to enable photo‐tunable modulation of CaV channel activity in excitable mammalian cells. This opto...
Mercury is a highly toxic environmental pollutant that negatively affects human health. Thus, an in vivo method for noninvasive imaging of mercury (II) and visualization of its accumulation within living systems would be advantageous. Herein, we describe a reaction-based bioluminescent probe for detection of mercury (II) in vitro and accumulation i...
As an important transition metal catalyst, palladium is extensively used in many areas including electronics industry, petroleum industry, automobile industry and fine chemicals engineering. However, it brings harm to the environment as well as people's health. Herein, we managed to introduce a butynyl group to 1,2-dioxetane developing a reaction-b...
Conventional analytical methods concerning the synthetic fluorescent probes have been extensively applied in the detection and visualization of biologically relevant chemical spices. Recently, with the rapid evolvement of chemical synthesis and nanotechnology, the utilization of fluorescent probes has expanded to fulfill the demands of clinical res...
Hypochlorous (HOCl) acid is generated as a defense tool in the immune system and plays a vital role in killing a wide range of pathogens. There is therefore great interest in developing fluorescent probes that can endogenously respond to the change in concentration of HOCl in vivo. To address this challenge, we here present a rapidly responding fluo...