Publications by authors named "Taijin Wang"

Selective poly(ADP-ribose) polymerase 1 (PARP1) inhibitors not only exhibit antitumor efficacy but also offer the potential to mitigate the toxicities typically associated with broader PARP inhibition. In this study, we designed and synthesized a series of small molecules targeting highly selective PARP1 inhibitors. Among these, demonstrated excellent selectivity to PARP1 along with the capability to effectively cross the blood-brain barrier (BBB).

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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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Deep generative models have become crucial tools in de novo drug design. In current models for multiobjective optimization in molecular generation, the scaffold diversity is limited when multiple constraints are introduced. To enhance scaffold diversity, we herein propose a local scaffold diversity-contributed generator (LSDC), which can be utilized to generate diverse lead compounds capable of satisfying multiple constraints.

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Higher physical activity (PA) levels will obtain more health-related benefits for children and adolescents with intellectual disabilities (ID). The mastery of fundamental movement skills (FMS) potentially correlates with PA. This study aimed to examine the associations of FMS with moderate-to-vigorous intensity physical activity (MVPA) levels in children and adolescents with moderate to severe ID.

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Children and adolescents with intellectual disabilities (ID) have low levels of physical activity (PA). Understanding factors influencing the PA participation of this population is essential to the design of effective interventions. The purposes of this study were to identify and map the barriers and facilitators of PA participation among children and adolescents with ID.

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In recent years, many different kinds of nonlinear optical materials have been applied to passively Q-switched solid-state lasers. However, the average output powers of these lasers are typically limited to 1 W due to the low damage threshold of the materials. In this study, a molybdenum-disulfide-doped glass-composite absorber was synthesized using the sol-gel method and spin-coating technique.

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In this work, a Tungsten disulfide (WS) reflective saturable absorber (SA) fabricated using the Langmuir-Blodgett technique was used in a solid state Nd:YVO laser operating at 1.34 µm. A Q-switched laser was constructed.

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Two-dimensional (2D) materials as saturable absorbers (SAs) have attracted intense interest for applications in pulsed laser generation because of their distinguishing optical properties. However, the existing methods of preparing SAs were insufficient. Here, we fabricated graphene oxide (GO) SAs by Langmuir-Blodgett (LB) methods for passively Q-switched Nd:YAG laser.

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Background/aims: Many tubulin inhibitors are in clinical use as anti-cancer drugs. In our previous study, a novel series of 4-substituted coumarins derivatives were identified as novel tubulin inhibitors. Here, we report the anti-cancer activity and underlying mechanism of one of the 4-substituted coumarins derivatives (SKLB060).

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Janus tyrosine kinase 3 (JAK3) is expressed in lymphoid cells and is involved in the signalling of T cell functions. The development of a selective JAK3 inhibitor has been shown to have a potential benefit in the treatment of autoimmune disorders. In this article, we developed the 4-aminopiperidine-based compound RB1, which was highly selective for JAK3 inhibition, with an IC of value of 40 nM, but did not inhibit JAK1, JAK2 or tyrosine kinase 2 (TYK2) at concentrations up to 5 µM.

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Here, we report the design and synthesis of pyrimidinyl heterocyclic compounds containing terminal electrophiles as irreversible covalent JAK3 inhibitors that exploit a unique cysteine (Cys909) residue in JAK3. Investigation of the structure-activity relationship utilizing kinase assays resulted in the identification of potent and selective JAK3 inhibitors such as T1, T8, T15, T22, and T29. Among them, T29 was verified as a promising JAK3 irreversible inhibitor that possessed the best bioactivity and selectivity against JAKs and kinases containing a cysteine in the residue analogous to Cys909 in JAK3, suggesting that covalent modification of this Cys residue allowed the identification of a highly selective JAK3 inhibitor.

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A series of novel 4-anilinoquinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, 14h exhibited the most potent cytotoxic activity with IC values ranging from 1.5 to 3.

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The cyclin dependent kinase CDK8, along with Med12 and Med13, form the kinase module of the Mediator complex. CDK8 expression associates with the activation of β-catenin in colon and gastric cancers. Herein, we applied docking-based virtual screening (VS) using the multiple crystal structures to identify several potent CDK8 inhibitors.

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Five new flavonoids, griffinones A-E (1-5), a new biphenylneolignan, griffilignan A (6) and ten known compounds were isolated from the n-hexane and EtOAc extracts of Millettia griffithii. The structures of the new compounds were determined by 1D and 2D NMR, and by HRMS. The anti-inflammatory activity of the isolated compounds was evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.

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Millepachine (MIL) was a novel chalcone that was separated from Millettia pachycarpa Benth (Leguminosae). We found MIL induced apoptosis through activating NF-κB pathway both in SK-OV-3 and A2780S cells. Western blot showed that MIL increased the levels of IKKα, p-IKKα/β, p-IκBα and NF-κB (p65) proteins, and decreased the expression of IκBα protein.

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Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor playing key roles in glucose and lipid homeostasis, and PPARγ ligands possess therapeutic potential in these as well as other areas. In this study, a series of phenylthiazole acids have been synthesized and evaluated for agonistic activity by a convenient fluorescence polarization-based PPARγ ligand screening assay. Compound 4t, as a potential PPARγ agonist with half maximal effective concentration (EC50) 0.

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In this paper, a series of novel 4-substituted coumarin derivatives were synthesized. Among these compounds 34, 39, 40, 43, 62, 65, and 67 exhibited significant antiproliferative activity toward a panel of tumor cell lines at subnanomolar IC50 values. Compound 65 showed potent antiproliferative ability (IC50 values of 7-47 nM) and retained full activity in multidrug resistant cancer cells.

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In the present study, a series of novel histone deacetylase (HDAC) inhibitors using the morpholinopurine as the capping group were designed and synthesized. Several compounds demonstrated significant HDAC inhibitory activities and antiproliferative effects against diverse human tumor cell lines. Among them, compound 10o was identified as a potent class I and class IIb HDAC inhibitor with good pharmaceutical profile and druglike properties.

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A novel series of substituted N-(4-(2-(4-benzylpiperazin-1-yl)ethoxy)phenyl)-N-methylquinazolin-4-amines were synthesized and evaluated for their in vitro antiproliferative activity. Among them, compound 7a exhibited the best potency, with IC50 values of 0.029-0.

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Free fatty acid receptor 2 (FFA2), also known as GPR43, is activated by short-chain fatty acids (SCFAs) that are mainly produced by the gut microbiota through the fermentation of undigested carbohydrates and dietary fibers. FFA2 currently appears to be a potential target in the management of obesity, diabetes, inflammatory diseases, and cancer. In the study, a series of novel phenylthiazole-carboxamido acid derivatives has been synthesized and evaluated as potential orthosteric FFA2 ligands for the study of structure-activity relationships.

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Novel selective histone deacetylase 6 (HDAC6) inhibitors using the quinazoline as the cap were designed, synthesized, and evaluated for HDAC enzymatic assays. N-Hydroxy-4-(2-methoxy-5-(methyl(2-methylquinazolin-4-yl)amino)phenoxy)butanamide, 23bb, was the most potent selective inhibitor for HDAC6 with an IC50 of 17 nM and showed 25-fold and 200-fold selectivity relative to HDAC1 and HDAC8, respectively. In vitro, 23bb presented low nanomolar antiproliferative effects against panel of cancer cell lines.

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Nicotinamide phosphoribosyltransferase (NAMPT), an enzyme taking part in main NAD biosynthetic pathway, is an attractive target for anticancer therapy. The purpose of our study is to find novel NAMPT inhibitors based on in silico drug discovery means including the generation of 3D-QSAR models, and virtual screening techniques. Firstly, ten pharmacophore models were generated by Catalyst/HypoGen algorithm.

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