A5052407554- Asymmetric Synthesis and Catalysis
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Synthesis and Catalytic Reactions
- Chemical Synthesis and Reactions
- Bioactive Compounds and Antitumor Agents
- Cancer Mechanisms and Therapy
- Pharmacological Receptor Mechanisms and Effects
- Liver physiology and pathology
- Asymmetric Hydrogenation and Catalysis
- Angiogenesis and VEGF in Cancer
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- Fibroblast Growth Factor Research
- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- PI3K/AKT/mTOR signaling in cancer
- interferon and immune responses
- Oxidative Organic Chemistry Reactions
- X-ray Diffraction in Crystallography
- Synthesis of Organic Compounds
- Crystallization and Solubility Studies
- Synthesis and pharmacology of benzodiazepine derivatives
- Protein Degradation and Inhibitors
Shanghai Institute of Materia Medica
2016-2025
Chinese Academy of Sciences
2016-2025
University of Chinese Academy of Sciences
2018-2025
University of Shanghai for Science and Technology
2022-2023
Nanjing University of Chinese Medicine
2022
East China University of Science and Technology
2008-2018
Institute of Medicinal Plant Development
2009-2012
University of New Mexico
2005-2008
Shanghai Institutes for Biological Sciences
2005-2008
Academia Sinica
2007
Conjugate addition reactions of a wide range nucleophilic enol species with enones, catalyzed by cinchona alkaloid derived thiourea organocatalyst, have been developed attending good yields and high enantioselectivities under mild reaction condition. The general method provides an efficient approach to the preparation versatile building blocks possessing various functional groups.
Background and Purpose— Activation of NMDA subtypes glutamate receptors is implicated in cell damage induced by ischemia as well for the establishment ischemic tolerance after preconditioning animal models. We investigated contributions NR2A- NR2B-containing to death a rat model transient global ischemia. Methods— Transient was produced rats 4-vessel occlusion. Neuronal injury analyzed Fluoro-Jade B Nissl staining. Phosphorylation CREB detected Western blotting immunohistochemistry. In situ...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 200 leading journals. To access the actual Abstract, please click on HTML or PDF.
Fleeting activation of NMDA receptors (NMDARs) induces long-term modification synaptic connections and refinement neuronal circuits, which may underlie learning memory contribute to pathogenesis a diversity neurological diseases, including epilepsy. Here, we found that NR2A NR2B subunit-containing NMDARs were coupled distinct intracellular signaling, resulting in differential BDNF expression extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Selective NR2A-containing increased...
A highly enantioselective conjugate addition of nitroalkanes to enones has been developed. The process is efficiently catalyzed by a simple chiral cyclohexanediamine-derived primary amine thiourea with broad substrate scope.
When isatin a cat! A highly efficient, cupreine-catalyzed, enantioselective Henry reaction of readily available isatins and nitroalkanes has been developed (see scheme). The products are produced in excellent yields good enantioselectivities under mild conditions without chromatography. utility the strategy demonstrated facile synthesis (S)-(−)-spirobrassinin need for protecting groups. Detailed facts importance to specialist readers published as "Supporting Information". Such documents...
Fibroblast growth factor receptors (FGFRs) are important targets for cancer therapy. Herein, we describe the design, synthesis, and biological evaluation of a novel series 1H-pyrazolo[3,4-b]pyridine derivatives as potent selective FGFR kinase inhibitors. On basis its excellent in vitro potency favorable pharmacokinetic properties, compound 7n was selected vivo showed significant antitumor activity FGFR1-driven H1581 xenograft model. These results indicated that would be promising candidate...
Abstract This study is intended to characterize the cellular target of gambogic acid (GA), a natural product isolated from gamboge resin Garcinia hurburyi tree, which possesses potent in vitro and vivo antitumor activities. The antiproliferative activity GA was further confirmed here panel human tumor cells multidrug-resistant cells. We found that significantly inhibited catalytic topoisomerase (Topo) II and, comparatively less extent, Topo I, without trapping stabilizing covalent...
The development of efficient methods for the facile construction important molecular frameworks is an goal in organic synthesis. Chiral 3-substituted phthalides are widely distributed a large collection natural products with broad, potent, and potentially path-pointing biological activities. In this investigation, we have uncovered unprecedented organocatalytic asymmetric aldol-lactonization reaction 2-formylbenzoic esters ketones/aldehydes convenient enantioenriched "privileged" scaffold....
Good neighbors: Cross-aldol reactions of isatins with aldehydes, catalyzed by (S)-pyrrolidine tetrazole are developed. In the process, two contiguous quaternary centers and one chiral carbon created simultaneously good efficiency.
Abstract Shikonin, a naphthoquinone pigment isolated from the Chinese herbal therapeutic, Zicao, has been shown to exhibit antioxidant and anticancer effects. In this study, its ability induce apoptosis in cultured Tca‐8113 oral cancer cells was studied. Treatment of with variety concentrations Shikonin (10–40 µm) resulted dose‐ time‐dependent sequences events marked by apoptosis, as loss cell viability, chromatin condensation, internucleosomal DNA fragmentation sub‐G1 phase accumulation....
Branch point: A simple primary amine thiourea catalyzed highly enantioselective conjugate addition of α,α-disubstituted aldehydes to maleimides has been developed. The biologically useful chiral disubstituted α-branched succinimides are attained with the generation two contiguous quaternary and/or tertiary stereogenic centers in one step excellent enantioselectivities and high yields under mild reaction conditions (see scheme).
Gambogic acid (GA) is a major active ingredient of gamboge, widely used traditional Chinese medicine that has been reported to be potent cytotoxic agent against some malignant tumors. Many studies have shown the NF-kappa B signaling pathway plays an important role in anti-apoptosis and drug resistance tumor cells during chemotherapy. In this study, effects mechanisms GA inhibitor celastrol on oral cancer were investigated.Three human squamous cell carcinoma lines, Tca8113, TSCC NT, treated...
PRMT5 plays important roles in diverse cellular processes and is upregulated several human malignancies. Besides, has been validated as an anticancer target mantle cell lymphoma. In this study, we found a potent selective inhibitor by performing structure-based virtual screening hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited broad selectivity against panel of other methyltransferases. direct binding to was surface plasmon resonance experiments, with Kd 0.987 μM....
Fibroblast growth factor receptor (FGFR) represents an attractive oncology target for cancer therapy in view of its critical role promoting formation and progression, as well causing resistance to approved therapies. In this article, we describe the identification potent pan-FGFR inhibitor (R)-21c (FGFR1–4 IC50 values 0.9, 2.0, 6.1 nM, respectively). Compound exhibited excellent vitro inhibitory activity against a panel FGFR-amplified cell lines. Western blot analysis demonstrated that...
Background: Liver cancer stem cells (LCSCs) are responsible for the initiation, progression and chemoresistance of liver cancer.However, no agent targeting LCSC is available in clinic to date.Here, we investigated effects protein arginine methyltransferase 5 (PRMT5), an epigenetic regulator, on LCSCs HCC using a novel PRMT5 inhibitor DW14800.Methods: Tumor spheroid formation culture was used enrich assess their self-renewal capability.Human alpha-1-antitrypsin (A1AT) ELISA, acetylated...
Stimulator of interferon gene (STING) is increasingly exploited for the potential in cancer immunotherapy, yet its mechanism activation remains not fully understood. Herein, we designed a novel STING agonist, designated as HB3089 that exhibits robust and durable anti-tumor activity tumor models across various types. Cryo-EM analysis reveals HB3089-bound human has structural changes similar to mutant V147L, constitutively activated identified patients with STING-associated vasculopathy onset...
1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enylfuran-2-caroxylate (SH-7), a new naphthoquinone compound, derived from shikonin, exhibited obvious inhibitory actions on topoisomerase II (Topo II) and I I), which were stronger than its mother compound shikonin. Notably, the SH-7's potency Topo was much that I. In addition, SH-7 significantly stabilized II-DNA cleavable complex elevated expression of phosphorylated-H2AX. The in vitro cell-based investigation...
Abstract The enantioselective conjugate addition of a variety ketones to nitroolefins has been developed. process is efficiently catalyzed by novel bifunctional sulfonamide primary amine in good yields and with levels enantioselectivity.
c-Met inhibitor JNJ38877605 has proven curative as an antitumor agent, while its clinical study was terminated due to renal toxicity. It reported that the toxicity caused by poor solubility of aldehyde oxidase (AO) metabolites. Therefore, blocking AO oxidation might diminish toxic metabolites and overcome Compound 3, metabolic site deuterated JNJ38877605, then synthesized target molecule. In vitro monkey liver S9 fraction incubation 3 manifested metabolite M2-2 significantly reduced, which...
Interleukin-1 receptor associated kinase 4 (IRAK4) is a promising therapeutic target for diffuse large B-cell lymphoma driven by MYD88 L265P mutant, acting both as and scaffolding protein downstream signaling molecules. While previous efforts to modulate IRAK4 activity with inhibitors alone displayed moderate efficacy, degradation may offer solution blocking capabilities. To this end, the potent degrader 9 was discovered, it effectively inhibited activation of NF-κB outperformed parent...