排序方式: 共有32条查询结果,搜索用时 203 毫秒
21.
Selness SR Boehm TL Walker JK Devadas B Durley RC Kurumbail R Shieh H Xing L Hepperle M Rucker PV Jerome KD Benson AG Marrufo LD Madsen HM Hitchcock J Owen TJ Christie L Promo MA Hickory BS Alvira E Naing W Blevis-Bal R Devraj RV Messing D Schindler JF Hirsch J Saabye M Bonar S Webb E Anderson G Monahan JB 《Bioorganic & medicinal chemistry letters》2011,21(13):4059-4065
A series of N-aryl pyridinone inhibitors of p38 mitogen activated protein (MAP) kinase were designed and prepared based on the screening hit SC-25028 (1) and structural comparisons to VX-745 (5). The focus of the investigation targeted the dependence of potency and metabolic stability on the benzyloxy connectivity, the role of the C-6 position and the substitution pattern on the N-phenyl ring. Further optimization produced the highly selective and potent pyridinones 2 and 3. These inhibitors exhibited activity in both acute and chronic models of inflammation. 相似文献
22.
JC polyomavirus (JCPyV) is a common human pathogen that results in a chronic asymptomatic infection in healthy adults. Under conditions of immunosuppression, JCPyV spreads to the central nervous system and can cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML), a disease for which there are no vaccines or antiviral therapies. Retro-2 is a previously identified small molecule inhibitor that was originally shown to block retrograde transport of toxins such as ricin toxin from endosomes to the Golgi apparatus and endoplasmic reticulum (ER), and Retro-2.1 is a chemical analog of Retro-2 that has been shown to inhibit ricin intoxication of cells at low nanomolar concentrations. Retro-2 has previously been shown to prevent retrograde transport of JCPyV virions to the ER, but the effect of Retro-2.1 on JCPyV infectivity is unknown. Here it is shown that Retro-2.1 inhibits JCPyV with an EC50 of 3.9 μM. This molecule inhibits JCPyV infection at dosages that are not toxic to human tissue culture cells. Retro-2.1 was also tested against two other polyomaviruses, the human BK polyomavirus and simian virus 40, and was also shown to inhibit infection at similar concentrations. Viral uncoating studies demonstrate that Retro-2.1 inhibits BKPyV infectivity in a manner similar to Retro-2. These studies demonstrate that improved analogs of Retro-2 can inhibit infection at lower dosages than Retro-2 and further optimization of these compounds may lead to effective treatment options for those suffering from JCPyV infection and PML. 相似文献
23.
Yulia Anita Muhammad Radifar Leonardus BS Kardono Muhammad Hanafi Enade P Istyastono 《Bioinformation》2012,8(19):901-906
Eugenol is an essential oil mainly found in the buds and leaves of clove (Syzygium aromaticum (L.) Merrill and Perry), which has
been reported to have activity on inhibition of cell proliferation and apoptosis induction in human MCF-7 breast cancer cells. This
biological activity is correlated to its activity as an estrogen receptor antagonist. In this article, we present the construction and
validation of structure-based virtual screening (SBVS) protocols to identify the potent estrogen receptor α (ER) antagonists. The
selected protocol, which gave acceptable enrichment factors as a virtual screening protocol, subsequently used to virtually screen
eugenol, its analogs and their dimers. Based on the virtual screening results, dimer eugenol of 4-[4-hydroxy-3-(prop-2-en-1-
yl)phenyl]-2-(prop-2-en-1-yl)phenol is recommended to be developed further in order to discover novel and potent ER antagonists. 相似文献
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25.
Background
The dynamic growing and shortening behaviors of microtubules are central to the fundamental roles played by microtubules in essentially all eukaryotic cells. Traditionally, microtubule behavior is quantified by manually tracking individual microtubules in time-lapse images under various experimental conditions. Manual analysis is laborious, approximate, and often offers limited analytical capability in extracting potentially valuable information from the data.Results
In this work, we present computer vision and machine-learning based methods for extracting novel dynamics information from time-lapse images. Using actual microtubule data, we estimate statistical models of microtubule behavior that are highly effective in identifying common and distinct characteristics of microtubule dynamic behavior.Conclusion
Computational methods provide powerful analytical capabilities in addition to traditional analysis methods for studying microtubule dynamic behavior. Novel capabilities, such as building and querying microtubule image databases, are introduced to quantify and analyze microtubule dynamic behavior.26.
The immunophenotype of HT29 human colon cancer cells implanted into severe combined immunodeficient mice was assessed in primary
tumours and their metastases in the lungs using an indirect immunohistochemical method. After primary tumours were surgically
removed, the metastases were given time to develop, thus paralleling the clinical situation. While vimentin was negative in
both primary and secondary tumours, E-cadherin was present as membrane-bound labelling in the primary tumours only. Whereas
the markers p53, MIB1, PCNA and CEA were consistently positive in both primary and metastatic tumours, CD44 variant 6 and
CA125 were negative in metastases but positive in the primary tumours. There was a significant increase in the percentage
of cells labelled for p53 in the primary tumours compared with the metastases. For the proliferation markers, there was no
significant difference in labelling between primary tumours and metastases for MIB1. Of the cytokeratins examined, CK 20 gave
the strongest and most consistent reaction in both primary and secondary tumours. The results indicate that, for certain immunohistochemical
markers, results are the same in both primary tumours and metastases. Hence, in these cases, antigens that are expressed on
the primary tumour as well as on the metastases can serve as target molecules for immunologically based forms of treatment
of metastases.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
27.
A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome 总被引:29,自引:24,他引:5
A model of DNA sequence evolution applicable to coding regions is
presented. This represents the first evolutionary model that accounts for
dependencies among nucleotides within a codon. The model uses the codon, as
opposed to the nucleotide, as the unit of evolution, and is parameterized
in terms of synonymous and nonsynonymous nucleotide substitution rates. One
of the model's advantages over those used in methods for estimating
synonymous and nonsynonymous substitution rates is that it completely
corrects for multiple hits at a codon, rather than taking a parsimony
approach and considering only pathways of minimum change between homologous
codons. Likelihood-ratio versions of the relative-rate test are constructed
and applied to data from the complete chloroplast DNA sequences of Oryza
sativa, Nicotiana tabacum, and Marchantia polymorpha. Results of these
tests confirm previous findings that substitution rates in the chloroplast
genome are subject to both lineage-specific and locus-specific effects.
Additionally, the new tests suggest tha the rate heterogeneity is due
primarily to differences in nonsynonymous substitution rates. Simulations
help confirm previous suggestions that silent sites are saturated, leaving
no evidence of heterogeneity in synonymous substitution rates.
相似文献
28.
M A Massa D P Spangler R C Durley B S Hickory D T Connolly B J Witherbee M E Smith J A Sikorski 《Bioorganic & medicinal chemistry letters》2001,11(13):1625-1628
A series of novel N,N-disubstituted trifluoro-3-amino-2-propanols has been prepared as potent inhibitors of cholesteryl ester transfer protein (CETP). Modifying the aromatic 3-tetrafluoroethoxy group in the lead molecule 1a with various heteroaryl moieties produced new 2-furyl analogues 2a,b with submicromolar potency in vitro. 相似文献
29.
30.