1,726,740 research outputs found
Design of dual ligands using excessive pharmacophore query alignment : from 7th German Conference on Chemoinformatics: 25 CIC-Workshop Goslar, Germany, 6 - 8 November 2011
No full textDual- or multi-target ligands have gained increased attention in the past years due to several advantages, including more simple pharmacokinetic and phamarcodynamic properties compared to a combined application of several drugs. Furthermore multi-target ligands often possess improved efficacy. We present a new approach for the discovery of dual-target ligands using aligned pharmacophore models combined with a shape-based scoring. Starting with two sets of known active compounds for each target, a number of different pharmacophore models is generated and subjected to pairwise graph-based alignment using the Kabsch-Algorithm. Since a compound may be able to bind to different targets in different conformations, the algorithm aligns pairs of pharmacophore models sharing the same features which are not necessarily at the exactly same spatial distance. Using the aligned models, a pharmacophore search on a multi-conformation-database is performed to find compounds matching both models. The potentially “dual” ligands are scored by a shape-based comparison with the known active molecules using ShaEP.
Using this approach, we performed a prospective fragment-based virtual screening for dual 5-LO/sEH inhibitors. Both enzymes play an important role in the arachidonic acid cascade and are involved in inflammatory processes, pain, cardiovascular diseases and allergic reactions. Beside several new selective inhibitors we were able to find a compound inhibiting both enzymes in low micromolar concentrations. The results indicate that the idea of aligned pharmacophore models can be successfully employed for the discovery of dual-target ligands
Mandurama photograph collection [2946] [picture] /
No full textAlso available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-an8526486-2946
U-2946: an ABC DLBCL cell line.
No full textA) heatmap of ABC/GC gene expression, data from expression array analysis. The majority of ten ABC and GC markers described by Ruminy et al. [33] class U-2946 as ABC DLBCL cell line. B) Applying the same set of marker genes, cell line U-2946 clustered together with described ABC DLBCL cell lines (red), not with GC cell lines (green) [5–9]. Cell line NU-DHL-1 (orange) was discordantly categorized by different authors [6,8]. We showed that subclone R1 of the ABC cell line U-2932 highly expressed various GC markers, absent from subclone R2 [34].</p
Block Card 2946 Wicklow Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch houses | 2946 Wicklow Drive (Toledo, Ohio) | attached garage | Dwelling | Old Orchard Addition, Fifth Extension (Toledo, Ohio) | Westgate Area (Toledo, Ohio
Green, Frank Henry (SC 2946)
Full text linkFinding aid and full text manuscript (Click on Additional Files below) for Manuscripts Small Collection 2946. “Mammoth Cave Stories – Mammoth Cave National Park,” by Frank Henry Green. A guide at the park from 1975-1986 and 2008-2009, Green includes narratives of cave tours, stories about other guides, and anecdotes relating to his work. Includes illustrations
Immunoprofile of patient and–derived cell line U-2946.
No full textImmunoprofile of patient and–derived cell line U-2946.</p
D-2946(8): 531 Douglas Drive, Logan, Utah, Unidentified residence
No full textD-2946(8): 531 Douglas Drive, Logan, Utah, Unidentified residenc
Block Card 2946 Darlington Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: English Cottage Style | 2946 Darlington Road (Toledo, Ohio) | Dwelling | Barton Place Addition (Toledo, Ohio) | Old Orchard Area (Toledo, Ohio
Diffuse Large B Cell Lymphoma Cell Line U-2946: Model for MCL1 Inhibitor Testing
No full textDiffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma worldwide. We describe the establishment and molecular characteristics of the DLBCL cell line U-2946. This cell line was derived from a 52-year-old male with DLBCL. U-2946 cells carried the chromosomal translocation t(8;14) and strongly expressed MYC, but not the mature B-cell lymphoma associated oncogenes BCL2 and BCL6. Instead, U-2946 cells expressed the antiapoptotic BCL2 family member MCL1 which was highly amplified genomically (14n). MCL1 amplification is recurrent in DLBCL, especially in the activated B cell (ABC) variant. Results of microarray expression cluster analysis placed U-2946 together with ABC-, but apart from germinal center (GC)-type DLBCL cell lines. The 1q21.3 region including MCL1 was focally coamplified with a short region of 17p11.2 (also present at 14n). The MCL1 inhibitor A-1210477 triggered apoptosis in U-2946 (MCL1pos/BCL2neg) cells. In contrast to BCL2pos DLBCL cell lines, U-2946 did not respond to the BCL2 inhibitor ABT-263. In conclusion, the novel characteristics of cell line U-2946 renders it a unique model system to test the function of small molecule inhibitors, especially when constructing a panel of DLBCL cell lines expressing broad combinations of antiapoptotic BCL2-family members
A Response to Mooi, Williams and Gill
Full text linkThis is the publisher's version, which the author has permission to share. The original version may be found at the following link: http://www.mapress.com/zootaxa/list/2011/2946.htm
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