Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport
A potent class of indolinyl-thiazole based inhibitors of cellular lipid uptake mediated by scavenger receptor, class B, type I (SR-BI) was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) in an assay measuring the...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2017
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| Online Access: | http://hdl.handle.net/1721.1/106868 https://orcid.org/0000-0003-2673-1672 https://orcid.org/0000-0003-4541-5181 |
| _version_ | 1826207413899886592 |
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| author | Dockendorff, Chris Faloon, Patrick W. Youngsaye, Willmen Nag, Partha P. Lewis, Timothy A. Pu, Jun Bennion, Melissa Negri, Joseph Paterson, Conor Lam, Garrett Dandapani, Sivaraman Perez, José R. Munoz, Benito Palmer, Michelle A. Schreiber, Stuart L. Yu, Miao Penman, Marsha L Nieland, Thomas J Krieger, Monty |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Dockendorff, Chris Faloon, Patrick W. Youngsaye, Willmen Nag, Partha P. Lewis, Timothy A. Pu, Jun Bennion, Melissa Negri, Joseph Paterson, Conor Lam, Garrett Dandapani, Sivaraman Perez, José R. Munoz, Benito Palmer, Michelle A. Schreiber, Stuart L. Yu, Miao Penman, Marsha L Nieland, Thomas J Krieger, Monty |
| author_sort | Dockendorff, Chris |
| collection | MIT |
| description | A potent class of indolinyl-thiazole based inhibitors of cellular lipid uptake mediated by scavenger receptor, class B, type I (SR-BI) was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) in an assay measuring the uptake of the fluorescent lipid DiI from HDL particles. This class of compounds is represented by ML278 (17–11), a potent (average IC[subscript 50] = 6 nM) and reversible inhibitor of lipid uptake via SR-BI. ML278 is a plasma-stable, noncytotoxic probe that exhibits moderate metabolic stability, thus displaying improved properties for in vitro and in vivo studies. Strikingly, ML278 and previously described inhibitors of lipid transport share the property of increasing the binding of HDL to SR-BI, rather than blocking it, suggesting there may be similarities in their mechanisms of action. |
| first_indexed | 2024-09-23T13:49:36Z |
| format | Article |
| id | mit-1721.1/106868 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:49:36Z |
| publishDate | 2017 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1068682022-10-01T17:22:16Z Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport Dockendorff, Chris Faloon, Patrick W. Youngsaye, Willmen Nag, Partha P. Lewis, Timothy A. Pu, Jun Bennion, Melissa Negri, Joseph Paterson, Conor Lam, Garrett Dandapani, Sivaraman Perez, José R. Munoz, Benito Palmer, Michelle A. Schreiber, Stuart L. Yu, Miao Penman, Marsha L Nieland, Thomas J Krieger, Monty Massachusetts Institute of Technology. Department of Biology Yu, Miao Penman, Marsha L Nieland, Thomas J Krieger, Monty A potent class of indolinyl-thiazole based inhibitors of cellular lipid uptake mediated by scavenger receptor, class B, type I (SR-BI) was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) in an assay measuring the uptake of the fluorescent lipid DiI from HDL particles. This class of compounds is represented by ML278 (17–11), a potent (average IC[subscript 50] = 6 nM) and reversible inhibitor of lipid uptake via SR-BI. ML278 is a plasma-stable, noncytotoxic probe that exhibits moderate metabolic stability, thus displaying improved properties for in vitro and in vivo studies. Strikingly, ML278 and previously described inhibitors of lipid transport share the property of increasing the binding of HDL to SR-BI, rather than blocking it, suggesting there may be similarities in their mechanisms of action. National Institutes of Health (U.S.) (Grants HL052212 and HL066105) 2017-02-06T16:04:44Z 2017-02-06T16:04:44Z 2015-02 2014-04 Article http://purl.org/eprint/type/JournalArticle 1948-5875 1948-5875 http://hdl.handle.net/1721.1/106868 Dockendorff, Chris et al. “Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport.” ACS Medicinal Chemistry Letters 6.4 (2015): 375–380. © 2015 American Chemical Society https://orcid.org/0000-0003-2673-1672 https://orcid.org/0000-0003-4541-5181 en_US http://dx.doi.org/10.1021/ml500154q ACS Medicinal Chemistry Letters Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) ACS |
| spellingShingle | Dockendorff, Chris Faloon, Patrick W. Youngsaye, Willmen Nag, Partha P. Lewis, Timothy A. Pu, Jun Bennion, Melissa Negri, Joseph Paterson, Conor Lam, Garrett Dandapani, Sivaraman Perez, José R. Munoz, Benito Palmer, Michelle A. Schreiber, Stuart L. Yu, Miao Penman, Marsha L Nieland, Thomas J Krieger, Monty Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport |
| title | Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport |
| title_full | Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport |
| title_fullStr | Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport |
| title_full_unstemmed | Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport |
| title_short | Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport |
| title_sort | indolinyl thiazole based inhibitors of scavenger receptor bi sr bi mediated lipid transport |
| url | http://hdl.handle.net/1721.1/106868 https://orcid.org/0000-0003-2673-1672 https://orcid.org/0000-0003-4541-5181 |
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