Institution
Torrey Pines Institute for Molecular Studies
Nonprofit•San Diego, California, United States•
About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: T cell & Antigen. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.
Topics: T cell, Antigen, Solid-phase synthesis, Cytotoxic T cell, Peptide
Papers published on a yearly basis
Papers
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TL;DR: A resorcinarene bearing four TEMPO units recognizes small molecules in solutions and binds to Na6(CO3, Na4SO4, Na2SO4 and Na2CO3 in solutions.
26 citations
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TL;DR: An efficient approach for the parallel solid phase synthesis of isoxazole and isoxzoline derivatives has been developed and presents a new alternative to the diversity oriented synthesis of disubstituted is oxazoles and isxazolines different from existing routes which are limited in structural diversity.
26 citations
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TL;DR: Pancreatic cancer cells are characterized by deregulated metabolic programs that facilitate growth and resistance to oxidative stress, and preferentially utilise mitochondria for cell proliferation and cell reprograming.
Abstract: Pancreatic cancer cells are characterized by deregulated metabolic programs that facilitate growth and resistance to oxidative stress. Among these programs, pancreatic cancers preferentially utiliz...
26 citations
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TL;DR: Using high-throughput screening against multi-drug resistant Pseudomonas aeruginosa, a polyamine scaffold is identified that has strong potential for the future development of novel and broadly active efflux pump inhibitors targeting multi- drug resistant bacterial infections.
Abstract: We have previously reported the use of combinatorial chemistry to identify broad-spectrum antibacterial agents. Herein, we extend our analysis of this technology toward the discovery of anti-resistance molecules, focusing on efflux pump inhibitors. Using high-throughput screening against multi-drug resistant Pseudomonas aeruginosa, we identified a polyamine scaffold that demonstrated strong efflux pump inhibition without possessing antibacterial effects. We determined that these molecules were most effective with an amine functionality at R1 and benzene functionalities at R2 and R3. From a library of 188 compounds, we studied the properties of 5 lead agents in detail, observing a fivefold to eightfold decrease in the 90% effective concentration of tetracycline, chloramphenicol, and aztreonam toward P. aeruginosa isolates. Additionally, we determined that our molecules were not only active toward P. aeruginosa, but toward Acinetobacter baumannii and Staphylococcus aureus as well. The specificity of our molecules to efflux pump inhibition was confirmed using ethidium bromide accumulation assays, and in studies with strains that displayed varying abilities in their efflux potential. When assessing off target effects we observed no disruption of bacterial membrane polarity, no general toxicity toward mammalian cells, and no inhibition of calcium channel activity in human kidney cells. Finally, combination treatment with our lead agents engendered a marked increase in the bactericidal capacity of tetracycline, and significantly decreased viability within P. aeruginosa biofilms. As such, we report a unique polyamine scaffold that has strong potential for the future development of novel and broadly active efflux pump inhibitors targeting multi-drug resistant bacterial infections.
26 citations
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TL;DR: Mouse pharmacokinetic studies revealed that potency would limit immediate cell- and rodent xenograft-based experiments aimed at validating this potential cancer metabolism-related target, and medicinal chemistry-based optimization resulted in the identification of multiple derivatives with >10-fold improvements in potency, as well as the identified of a tryptamine-based series of GOT1 inhibitors.
26 citations
Authors
Showing all 2327 results
Name | H-index | Papers | Citations |
---|---|---|---|
Eric J. Topol | 193 | 1373 | 151025 |
John R. Yates | 177 | 1036 | 129029 |
George F. Koob | 171 | 935 | 112521 |
Ian A. Wilson | 158 | 971 | 98221 |
Peter G. Schultz | 156 | 893 | 89716 |
Gerald M. Edelman | 147 | 545 | 69091 |
Floyd E. Bloom | 139 | 616 | 72641 |
Stuart A. Lipton | 134 | 488 | 71297 |
Benjamin F. Cravatt | 131 | 666 | 61932 |
Chi-Huey Wong | 129 | 1220 | 66349 |
Klaus Ley | 129 | 495 | 57964 |
Nicholas J. Schork | 125 | 587 | 62131 |
Michael Andreeff | 117 | 959 | 54734 |
Susan L. McElroy | 117 | 570 | 44992 |
Peter E. Wright | 115 | 444 | 55388 |