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: Galactosyltransferase and β-galactosidase have been investigated with regard to their acceptor specificity and used in the synthesis of galactosides using 5-thioglucose, deoxyazaglucose and modified N-acetylglucosamine and glucose derivatives as acceptors.
32 citations
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TL;DR: By characterizing the binding constants for all of the hits that arise from a screen, structure–activity relationship (SAR) data can be obtained to inform the design of “derivative libraries” of a primary hit that can then be screened under more demanding conditions to obtain improved compounds.
Abstract: Primary hits that arise from screening one bead one compound (OBOC) libraries against a target of interest rarely have high potency. However, there has been little work focused on the development of an efficient workflow for primary hit improvement. In this study, we show that by characterizing the binding constants for all of the hits that arise from a screen, structure–activity relationship (SAR) data can be obtained to inform the design of “derivative libraries” of a primary hit that can then be screened under more demanding conditions to obtain improved compounds. Here, we demonstrate the rapid improvement of a primary hit against matrix metalloproteinase-14 using this approach.
32 citations
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29 Oct 2003TL;DR: In this article, a trimeric polypeptide comprising a trimerising domain and three monomers with binding members capable of binding trimeric cytokines was provided, such that upon binding, all receptor binding sites of the trimeria are substantially blocked, and hence the potential biological activity of the trimmederia is suppressed.
Abstract: The present invention pertains to the provision of trimeric binding units which bind to trimeric cytokines. In particular there is provided a trimeric polypeptide comprising a trimerising domain and three monomers with binding members capable of binding a trimeric cytokine. Preferably , the trimeric binding units bind in a manner such that upon binding, all receptor binding sites of the trimeric cytokine are substantially blocked, and hence the potential biological activity of the trimeric cytokine is suppressed. In one aspect the invention relates to trimeric binders capable of binding to trimeric cytokines of the Tumor necrosis factor ligand superfamily, such as TNF, TRAIL, RANKL, TWEAK, APRIL and BAFF.
32 citations
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TL;DR: Introduction of the amino group into the heterocyclic core decreased the antimitotic antitubulin effect of pyrazoles, triazoles, and to a lesser degree of 4,5-diarylisoxazole, whereas potency of the respective 3,4-diariesoxazoles was increased.
Abstract: A series of both novel and reported combretastatin analogues, including diarylpyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles, were synthesized via improved protocols to evaluate their antimitotic antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure–activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0.25, 1, and 0.5 nM, respectively. These agents exhibited comparable cytotoxicity against human cancer cells. Structure–activity relationship studies revealed that compounds substituted with 3,4,5-trimethoxyphenyl ring A and 4-methoxyphenyl ring B displayed the highest activity. 3-Hydroxy group in the ring B was essential for the antiproliferative activity in the diarylisoxazole series, whereas it was not required for potency of diar...
32 citations
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TL;DR: These compounds were also highly selective when tested against a panel of 30 proteases, which, in combination with a good CYP inhibition profile, suggested low off-target toxicity and drug–drug interactions in humans.
Abstract: Matrix metalloproteinase 13 (MMP-13) has been shown to be the main collagenase responsible for degradation of articular cartilage during osteoarthritis and therefore represents a target for drug development. As a result of high-throughput screening and structure-activity relationship studies, we identified a novel, highly selective class of MMP-13 inhibitors (compounds 1 (Q), 2 (Q1), and 3 (Q2)). Mechanistic characterization revealed a noncompetitive nature of these inhibitors with binding constants in the low micromolar range. Crystallographic analyses revealed two binding modes for compound 2 in the MMP-13 S1' subsite and in an S1/S2* subsite. Type II collagen- and cartilage-protective effects exhibited by compounds 1, 2, and 3 suggested that these compounds might be efficacious in future in vivo studies. Finally, these compounds were also highly selective when tested against a panel of 30 proteases, which, in combination with a good CYP inhibition profile, suggested low off-target toxicity and drug-drug interactions in humans.
32 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 |