- Development of sulfonamide AKT PH domain inhibitors
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Disruption of the phosphatidylinositol 3-kinase/AKT signaling pathway can lead to apoptosis in cancer cells. Previously we identified a lead sulfonamide that selectively bound to the pleckstrin homology (PH) domain of AKT and induced apoptosis when present at low micromolar concentrations. To examine the effects of structural modification, a set of sulfonamides related to the lead compound was designed, synthesized, and tested for binding to the expressed PH domain of AKT using a surface plasmon resonance-based competitive binding assay. Cellular activity was determined by means of an assay for pAKT production and a cell killing assay using BxPC-3 cells. The most active compounds in the set are lipophilic and possess an aliphatic chain of the proper length. Results were interpreted with the aid of computational modeling. This paper represents the first structure-activity relationship (SAR) study of a large family of AKT PH domain inhibitors. Information obtained will be used in the design of the next generation of inhibitors of AKT PH domain function.
- Ahad, Ali Md.,Zuohe, Song,Du-Cuny, Lei,Moses, Sylvestor A.,Zhou, Li Li,Zhang, Shuxing,Powis, Garth,Meuillet, Emmanuelle J.,Mash, Eugene A.
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supporting information; experimental part
p. 2046 - 2054
(2011/05/05)
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- MODULATORS OF IMMUNOINHIBITORY RECEPTOR PD-1, AND METHODS OF USE THEREOF
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Disclosed are an assay to identify modulators of the PD-1 :PD-L pathway and PD-1 :PD-L pathway modulators, e.g., compounds and pharmaceutical compositions thereof. Methods for treating diseases influenced by modulation of the PD-1 :PD-L pathway such as, for example, autoimmune diseases, inflammatory disorders, allergies, transplant rejection, cancer, immune deficiency, and other immune system-related disorders, are also disclosed.
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Page/Page column 52
(2011/07/30)
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- SMALL MOLECULE INHIBITORS OF THE PLECKSTRIN HOMOLOGY DOMAIN AND METHODS FOR USING SAME
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Pleckstrin homology domain binding compounds, pharmaceutical compositions including such compounds, and methods for their use are described herein.
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Page/Page column 90
(2009/12/02)
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- Process for formulating a synthetic drug for use in animal feed, and resulting formulation
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A method of formulating a synthetic drug for use in animal feed, for the purpose of reducing carry-over of the synthetic drug to subsequent lots of animal feed in the feed mill.
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