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排序方式: 共有342条查询结果,搜索用时 15 毫秒
1.
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
2.
R Hui JR Ball RD Macmillan FS Kenny OW Prall DH Campbell AL Cornish RA McClelland RJ Daly JF Forbes RW Blamey EA Musgrove JF Robertson RI Nicholson RL Sutherland 《Canadian Metallurgical Quarterly》1998,17(8):1053-1059
The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification. 相似文献
3.
The optical properties of gold nanoparticles have been known for a number of years and recent advances in laser power have now allowed the non-linear optical properties to be studied. In this short review paper, the various theories that have been used to describe the optical properties of gold nanoparticles are presented. Methods of preparing gold nanoparticles in glasses are explained briefly, as well as characterization techniques. The optical properties of gold nanoparticles are reviewed, as well as the effects of particle size, shape, concentration and c. 相似文献
4.
A. H. Moinuddin Ahmed Lesley S. Dent Glasser 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》1973,23(6):457-463
α-BaO.Al2O3.4H2O has been synthesised and studied by infrared, X-ray and thermal analytical techniques. The compound of approximate formula BaO.Al2O3.0.5H2O, described in Part III, forms as a dehydration product, and appears to be identical with the compound β-BAH2 described by other workers. A possible explanation for the discrepancy in water content is discussed. 相似文献
5.
M. Hossein Nouri-Sorkhabi Lesley C. Wright David R. Sullivan Philip W. Kuchel 《Lipids》1996,31(7):765-770
31P Nuclear magnetic resonance (NMR) spectra of human erythrocyte lysates dissolved in sodium cholate were acquired. The narrow
resonances of phospholipids were mostly well resolved, allowing identification and accurate quantitative analysis of phospholipid
classes of the erythrocyte membranes. The ether-linked phosphatidylethanolamine components of the erythrocyte membranes were
identified, based on the removal of plasmalogens by acidolysis and of diacyl phospholipid species by degradation using phospholipase
A1. It was also shown that the introduction of double bonds on the acyl chains of phosphatidylcholine shifted the31P NMR resonances to lower frequencies. Quantitative analyses of phospholipids from the spectra were based on their apparent
molar concentrations. The recoveries of phospholipids from erythrocytes were significantly higher than those using conventional
extraction procedures. 相似文献
6.
The effect of trap design, trap color, and a mixture of isothiocyanates on the capture of Ceutorhynchus assimilis (Paykull) was studied in a series of field experiments. Unbaited yellow water traps, a yellow sticky box trap, and a yellow sticky card trap, mounted vertically, or at 45° to the vertical with the yellow card facing upwards were effective for capturing seed weevils, but a horizontal yellow sticky card trap caught few. White, green, and black traps were unattractive. During migratory periods, trap catch could be enhanced two to four times with a lure consisting of a mixture of allyl, 3-butenyl, 4-pentenyl, and 2-phenylethyl isothiocyanates, but this bait did not attract in a trap with ineffective design. The sticky card trap, mounted at 45° to the vertical and baited with the isothiocyanate mixture, may be useful for monitoring movement of C. assimilis during migratory periods. However, during the colonization phase, lures of either a mixture of isothiocyanates or of allyl isothiocyanate alone were not attractive. 相似文献
7.
Angelika Ziegler Sybil M. Macintosh Lesley Torrance William Simon Antony R. Slabas 《Lipids》1997,32(8):805-809
Purified Brassica napus enoyl acyl carrier protein reductase (ENR) was used to select specific antibodies from a library of antibody fragments, single-chain
Fv (scFv), displayed on filamentous phage. Analysis of the selected clones by BstNl fingerprinting and nucleotide sequencing showed that the scFv were derived from three different human VH germline genes. The binding specificities were confirmed by Western blots and ELISA. The scFv preparations reacted with B. napus ENR, but not with β-keto reductase, nor enoyl reductase from Escherichia coli. Analysis of fragments generated by CNBr treatment indicates that the scFv 3.13 recognizes an epitope located within the n-terminal 80 amino acids of the enzyme molecule. The scFv were used to detect ENR directly in extracts of B. napus seeds. 相似文献
8.
9.
Prior research has shown that people are likely to skim information presented digitally with the resultant deleterious effect on accurate mental models of the text. Teaching monitoring strategies and presenting text with adjunct questions are effective strategies for improving the mental models of readers of scientific text, but the two strategies have not been directly compared for studying text read from a computer screen. In the present study, participants were individually tested in two experiments in which they studied computer-based text on the heart and circulatory system while either reading the text with no interruption, answering adjunct inference questions, answering adjunct factual questions, or answering prompts for global or specific monitoring. Reading time was untimed but looking back was not available. Prompting for global monitoring was most effective for improvement of mental models as measured by scores in diagram drawing, concept map construction, factual memory, and generating inferences. Further, global monitoring did not require more time-on-task than the other methods. 相似文献
10.