The overall goal of this project is to identify inhibitors and use small molecules to analyze the mechanism of the HDL receptor called Scavenger Receptor, class B, type I (SR-BI). SR-BI was the first high density lipoprotein (HDL, "good" cholesterol) receptor identified. It controls the structure and composition of plasma HDL, and levels and fates of HDL cholesterol, including delivery to the more ..
Table of Contents
Target
| Sequence: Murine scavenger receptor B1 Protein Family: CD36 family Gene:SCARB1 |
Depositor Specified Assays
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| AID | Name | Type | Comment |
|---|---|---|---|
| 488896 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_SinglePoint_HTS_Activity | screening | 177227 hts compounds at singlepoint in DiI-HDL Cell Based Assay measuring activity |
| 493194 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_CherryPick_Activity | confirmatory | 473 cherrypick compounds at dose in DiI-HDL Cell Based Assay measuring activity set 1 |
| 540246 | HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity | confirmatory | 65 drypowder compounds at dose in 02 Cytotoxicity Assay in ldlA[SRB1] cells measuring activity |
| 540326 | DiI Quencher Assay Measured in Biochemical System Using Plate Reader - 2085-08_Inhibitor_Dose_CherryPick_Activity | confirmatory | 472 cherrypick compounds at dose in 08 DiI Quencher Assay measuring activity |
| 540354 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity | confirmatory | 65 drypowder compounds at dose in 01 DiI-HDL Cell Based Assay measuring activity |
| 588392 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | 31 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 2 |
| 588403 | DiI Quencher Assay Measured in Biochemical System Using Plate Reader - 2085-08_Inhibitor_Dose_DryPowder_Activity | confirmatory | 31 drypowder compounds at dose in 08 DiI Quencher Assay measuring activity |
| 588553 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set3 | confirmatory | 32 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 3 |
| 588548 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set4 | confirmatory | 32 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 4 |
| 588833 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set7 | confirmatory | 588833#3 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 7 |
| 588829 | HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | 17 drypowder compounds at dose in Cytotoxicity Assay in ldlA[SRB1] cells measuring activity set 2 |
| 588830 | HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-11_Inhibitor_Dose_DryPowder_Activity | confirmatory | 65 drypowder compounds at dose in 11 3 hour cytotoxicity assay measuring activity |
| 588831 | HDL Inhib: Reversibility Measured in Cell-Based System Using Plate Reader - 2085-14_Inhibitor_Dose_DryPowder_Activity | confirmatory | 3 drypowder compounds at dose in 14 DiI-HDL Reversibility Assay measuring activity |
| 602126 | HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set5 | confirmatory | 137 drypowder compounds at dose in Cytotoxicity Assay in ldlA[SRB1] cells measuring activity set 5 |
| 602134 | HDL Counter Assay: Tf Endo Assay Measured in Cell-Based System Using Plate Reader - 2085-04_Inhibitor_Dose_DryPowder_Activity | confirmatory | 13 drypowder compounds at dose in 04 Transferrin Endocytosis Assay measuring activity |
| 602154 | HDL Inhib: Reversibility Measured in Cell-Based System Using Plate Reader - 2085-15_Inhibitor_Dose_DryPowder_Activity | confirmatory | 3 drypowder compounds at dose in 15 Extended reversibility DiI-HDL uptake Assay measuring activity |
| 588836 | HDL Inhib: Activity in wild type cell line Measured in Cell-Based System Using Scintillation - 2085-12_Inhibitor_SinglePoint_DryPowder_Activity | other | 5 drypowder compounds at singlepoint in 12 Radiolabeled HDL uptake in wild type SR-BI cells measuring activity |
| 588837 | HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Scintillation - 2085-13_Inhibitor_SinglePoint_DryPowder_Activity | other | 5 drypowder compounds at singlepoint in 13 Radiolabeled uptake of HDL in C384S mutant SR-BI cells measuring activity |
| 588842 | HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set4 | confirmatory | 23 drypowder compounds at dose in Cytotoxicity Assay in ldlA[SRB1] cells measuring activity set 4 |
| 588843 | HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Plate Reader - 2085-10_Inhibitor_SinglePoint_DryPowder_Activity | other | 31 drypowder compounds at singlepoint in 10 Cholesterol efflux assay with C384S Mutant measuring activity |
| 602155 | Liposome Uptake Assay Measured in Biochemical System Using Scintillation - 2085-16_Inhibitor_Dose_DryPowder_Activity | other | 4 drypowder compounds at dose in 16 Liposome Uptake Assay measuring activity |
| 602152 | HDL MOA Assay: Efflux Assay Measured in Cell-Based System Using Plate Reader - 2085-06_Inhibitor_Dose_DryPowder_Activity | other | 2 drypowder compounds at dose in 06 Cholesterol Efflux Assay measuring activity |
| 602138 | HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Plate Reader - 2085-10_Inhibitor_Dose_DryPowder_Activity | other | 2 drypowder compounds at dose in 10 Cholesterol efflux assay with C384S Mutant measuring activity |
| 588754 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set5 | confirmatory | 35 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 5 |
| 588818 | HDL MOA Assay: Efflux Assay Measured in Cell-Based System Using Plate Reader - 2085-06_Inhibitor_SinglePoint_DryPowder_Activity | other | 5 drypowder compounds at singlepoint in 06 Cholesterol Efflux Assay measuring activity |
| 588828 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set6 | confirmatory | 17 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 6 |
| 588826 | HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set3 | confirmatory | 37 drypowder compounds at dose in Cytotoxicity Assay in ldlA[SRB1] cells measuring activity set 3 |
| 588825 | HDL Uptake counterscreen Measured in Cell-Based System Using Plate Reader - 2085-07_Inhibitor_Dose_DryPowder_Activity | confirmatory | 17 drypowder compounds at dose in 07 HDL Uptake Activation Counterscreen measuring activity |
| 588777 | HDL Orthogonal Assay: Alexa 488-HDL Measured in Cell-Based System Using Plate Reader - 2085-03_Inhibitor_Dose_DryPowder_Activity | confirmatory | 65 drypowder compounds at dose in 03 Alexa-488 labeled HDL Uptake Assay measuring activity |
| 588810 | HDL Orthogonal Assay: Alexa 488-HDL Measured in Cell-Based System Using Plate Reader - 2085-03_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | 35 drypowder compounds at dose in Alexa-488 labeled HDL Uptake Assay measuring activity set 2 |
| 624015 | HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Plate Reader - 2085-10_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | |
| 624024 | HDL Orthogonal Assay: Alexa 488-HDL Measured in Cell-Based System Using Plate Reader - 2085-03_Inhibitor_Dose_DryPowder_Activity_Set3 | confirmatory | |
| 624022 | HDL Inhib: Activity in wild type cell line Measured in Cell-Based System Using Scintillation - 2085-12_Inhibitor_Dose_DryPowder_Activity | confirmatory | |
| 602285 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set8 | confirmatory | |
| 623880 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set9 | confirmatory | |
| 624026 | HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set7 | confirmatory | |
| 624029 | HTS using DiI-HDL to assay lipid transfer in ldlA[SR-BI] cells Measured in Cell-Based System Using Plate Reader - 2085-01_Inhibitor_Dose_DryPowder_Activity_Set10 | confirmatory | |
| 624007 | HDL Uptake counterscreen Measured in Cell-Based System Using Plate Reader - 2085-07_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory | |
| 624010 | HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Scintillation - 2085-13_Inhibitor_Dose_DryPowder_Activity | confirmatory | |
| 623895 | HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set6 | confirmatory | |
| 624017 | HDL MOA Assay: Efflux Assay Measured in Cell-Based System Using Plate Reader - 2085-06_Inhibitor_Dose_DryPowder_Activity_Set2 | confirmatory |
Description:
Primary Collaborators:
Monty Krieger,MIT,krieger@mit.edu
Miao Yu,MIT,miaoyu@mit.edu
Project Goal:
The overall goal of this project is to identify inhibitors and use small molecules to analyze the mechanism of the HDL receptor called Scavenger Receptor, class B, type I (SR-BI). SR-BI was the first high density lipoprotein (HDL, "good" cholesterol) receptor identified. It controls the structure and composition of plasma HDL, and levels and fates of HDL cholesterol, including delivery to the liver and steroidogenic tissues. SR-BI binds HDL and functions i) as a cell surface transporter to move cholesterol or its esters into or out of cells and ii) as a signaling receptor to control cell function. It also can interact with and/or transport a plethora of other ligands.
Keywords: HDL, cholesterol metabolism, SR-BI, Scavenger receptor
Biological Relevance: Developing tools to permit the analysis of SR-BI function and mechanism of action (see below), as well as the manipulation of SR-BI's activity in vitro and in vivo, will have significant impact on our understanding of diverse areas of physiology and pathophysiology of considerable medical importance. Indeed, recent disappointments in attempts to develop HDL-focused pharmaceutical agents with other molecular targets highlight the importance of developing a deeper and broader understanding of all aspects of HDL metabolism, including those mediated by SR-BI. Pharmacologic agents that modulate SR-BI activity have potential clinical applicability (inhibitors that block cellular uptake of pathogens (e.g., HCV) and activators that stimulate atheroprotective lipoprotein metabolism), as well as their use as probes to understand the molecular mechanisms underlying SR-BI's multiple activities. Given the central role of SR-BI in lipid transfer and metabolism, both activators and inhibitors of SR-BI function will be useful tools to further probe the mechanism of SR-BI.
Monty Krieger,MIT,krieger@mit.edu
Miao Yu,MIT,miaoyu@mit.edu
Project Goal:
The overall goal of this project is to identify inhibitors and use small molecules to analyze the mechanism of the HDL receptor called Scavenger Receptor, class B, type I (SR-BI). SR-BI was the first high density lipoprotein (HDL, "good" cholesterol) receptor identified. It controls the structure and composition of plasma HDL, and levels and fates of HDL cholesterol, including delivery to the liver and steroidogenic tissues. SR-BI binds HDL and functions i) as a cell surface transporter to move cholesterol or its esters into or out of cells and ii) as a signaling receptor to control cell function. It also can interact with and/or transport a plethora of other ligands.
Keywords: HDL, cholesterol metabolism, SR-BI, Scavenger receptor
Biological Relevance: Developing tools to permit the analysis of SR-BI function and mechanism of action (see below), as well as the manipulation of SR-BI's activity in vitro and in vivo, will have significant impact on our understanding of diverse areas of physiology and pathophysiology of considerable medical importance. Indeed, recent disappointments in attempts to develop HDL-focused pharmaceutical agents with other molecular targets highlight the importance of developing a deeper and broader understanding of all aspects of HDL metabolism, including those mediated by SR-BI. Pharmacologic agents that modulate SR-BI activity have potential clinical applicability (inhibitors that block cellular uptake of pathogens (e.g., HCV) and activators that stimulate atheroprotective lipoprotein metabolism), as well as their use as probes to understand the molecular mechanisms underlying SR-BI's multiple activities. Given the central role of SR-BI in lipid transfer and metabolism, both activators and inhibitors of SR-BI function will be useful tools to further probe the mechanism of SR-BI.
Additional Information
Grant Number: 2 R01 HL052212-11
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