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排序方式: 共有3123条查询结果,搜索用时 301 毫秒
11.
Dr. Lina Liang Tong-You Wade Wei Pei-Yu Wu Wouter Herrebout Ming-Daw Tsai Prof. Stéphane P. Vincent 《Chembiochem : a European journal of chemical biology》2020,21(20):2982-2990
d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant. 相似文献
12.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
13.
Steffen Vojacek Lukas Schulig Nathalie Wössner Norman Geist Prof. Dr. Walter Langel Prof. Dr. Manfred Jung Prof. Dr. Dennis Schade Prof. Dr. Andreas Link 《ChemMedChem》2019,14(8):853-864
Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC50 value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling. 相似文献
14.
Dr. Hui Qiu Richard Caldwell Dr. Lesley Liu-Bujalski Dr. Andreas Goutopoulos Reinaldo Jones Justin Potnick Dr. Brian Sherer Dr. Andrew Bender Dr. Roland Grenningloh Dr. Daigen Xu Dr. Anna Gardberg Dr. Igor Mochalkin Dr. Theresa Johnson Dr. Ariele Viacava Follis Jared Head Dr. Federica Morandi 《ChemMedChem》2019,14(2):217-223
Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. 相似文献
15.
J. Tritthart 《Cement and Concrete Research》2003,33(6):829-834
Surface-applied corrosion inhibitors are a kind of repair material and usually contain an aminoalcohol and a component forming a salt with the aminoalcohol. According to the manufacturers, this type of inhibitor penetrates very rapidly into concrete; however, the transport mechanisms have not been sufficiently investigated so far. The major part of the study therefore focused on the transport of the ingredients of an inhibitor in cement paste and concrete, which contained an aminoalcohol and a phosphorous compound. It has been shown that the latter forms an insoluble calcium salt in the environment of cement and precipitates quantitatively. It is thus unable to penetrate from the outside into the alkaline concrete zone and cannot develop its inhibiting effect there. The aminoalcohol, on the other hand, is not bound by cement, but remains largely dissolved in the pore liquid, thus providing optimal conditions for high mobility. The analysis of the transport mechanisms involved has revealed that diffusion in the dissolved state is by far the most efficient transport mechanism. While basically the transport of the aminoalcohol via the gaseous phase is possible, it does play an inferior role only. Surprisingly, the substance had hardly been absorbed by concrete by capillary suction, but at first remained close to the concrete surface. 相似文献
16.
ABSTRACT: :
Soybeans ( Glycine max ) were soaked and ground to obtain soymilk. The soymilk was cooked in an open tank and held at 85 to 90 deg;C. Yuba films were picked up in 20 min intervals and dried for 20 min. Yuba films were soaked in chicken-flavor solutions (25% and 35%), and baking soda (BS) solutions (0%, 1%, 2%, and 3% BS), and cooked at 100 °C for 30 min, 60 min, and 90 min. TIA decreased (p < 0.05) with the increase of heating time and BS concentration. In vitro protein digestibility (IVPD) decreased with heating time and BS concentration (p < 0.05). Sensory characteristics were affected by flavor concentration. By using 0% BS, 25% of the chicken flavor concentration, and a short heating time method, meat-like products with low TIA, high IVPD, and good sensory characteristics were obtained. 相似文献
Soybeans ( Glycine max ) were soaked and ground to obtain soymilk. The soymilk was cooked in an open tank and held at 85 to 90 deg;C. Yuba films were picked up in 20 min intervals and dried for 20 min. Yuba films were soaked in chicken-flavor solutions (25% and 35%), and baking soda (BS) solutions (0%, 1%, 2%, and 3% BS), and cooked at 100 °C for 30 min, 60 min, and 90 min. TIA decreased (p < 0.05) with the increase of heating time and BS concentration. In vitro protein digestibility (IVPD) decreased with heating time and BS concentration (p < 0.05). Sensory characteristics were affected by flavor concentration. By using 0% BS, 25% of the chicken flavor concentration, and a short heating time method, meat-like products with low TIA, high IVPD, and good sensory characteristics were obtained. 相似文献
17.
Ramazan Kahraman 《Journal of Materials Engineering and Performance》2002,11(1):46-50
The objective of this study was to evaluate the effectiveness of sodium benzoate as an inhibitor to slow down or prevent atmospheric
corrosion/discoloration of the local mild steel during storage in the Arabian Gulf region. Test specimens were prepared from
locally produced reinforcing steel products. The inhibitor solution was applied on steel specimens at a concentration of 100
mM for 1 day at room temperature. Wooden exposure racks were used to hold as-received and inhibitor-treated specimens during
atmospheric exposure for different periods. Corrosion was evaluated through weight loss determination and electrochemical
technique. As expected, the Arabian Gulf atmosphere was corrosive on the as-received local mild steel. On the other hand,
treatment of steel with sodium benzoate lowered its corrosion rate during initial days of its exposure to atmosphere. However,
atmospheric corrosion inhibition performance of sodium benzoate deteriorated with exposure time after 30 or more days of atmospheric
exposure, and the corrosion rates of sodium benzoate-treated specimens reached that of the unprotected specimens at the end
of 90 days of atmospheric exposure. 相似文献
18.
19.
Yu. V. Balaban-Irmenin N. G. Fokina 《Power Technology and Engineering (formerly Hydrotechnical Construction)》2007,41(5):306-312
The effect of internal-corrosion inhibitors on heating-system pipelines is investigated. Tests were conducted on a testing
device for polarization measurements under conditions corresponding to the Rostov Heat-Supply System. The concentration of
OEDP-zinc, which provides a high degree of protection from general corrosion, is determined. The reagent has been successfully
incorporated into the Rostov No. 2 TPP.
__________
Translated from élektricheskie Stantsii, No. 7, July 2007, pp. 37–43. 相似文献
20.
Yu. V. Balaban-Irmenin N. G. Fokina 《Power Technology and Engineering (formerly Hydrotechnical Construction)》2007,41(4):228-232
The reliability of heat-supply systems is determined primarily by internal corrosion of the pipelines. The concentration of
oxygen in the water exerts a major influence on the corrosion. In systems with a standard oxygen content, OéDF-Zn is a highly
effective corrosion inhibitor. However, there are systems in which the quality of deaeration of the make-up water of the heat-supply
system is low (or deaeration is nonexistent), and the concentration of oxygen is considerably above the standard value. Classed
among these systems, for example, are the HWS systems, which are incorporated into closed heat-supply systems. The oxygen
concentration in these systems is analyzed to assess the situation.
__________
Translated from élektricheskie Stantsii, No. 6, June 2007, pp. 35–39. 相似文献