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BioAssay: AID 488952

Broad Institute Inihibitors of the HDL Receptor, SR-BI Inhibitors Probe Project

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 ..
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AID: 488952
Data Source: Broad Institute (2085_Inhibitor_Project)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2010-10-27
Modify Date: 2011-12-19
Target
Depositor Specified Assays
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AIDNameTypeComment
488896HTS 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_Activityscreening177227 hts compounds at singlepoint in DiI-HDL Cell Based Assay measuring activity
493194HTS 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_Activityconfirmatory473 cherrypick compounds at dose in DiI-HDL Cell Based Assay measuring activity set 1
540246HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activityconfirmatory65 drypowder compounds at dose in 02 Cytotoxicity Assay in ldlA[SRB1] cells measuring activity
540326DiI Quencher Assay Measured in Biochemical System Using Plate Reader - 2085-08_Inhibitor_Dose_CherryPick_Activityconfirmatory472 cherrypick compounds at dose in 08 DiI Quencher Assay measuring activity
540354HTS 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_Activityconfirmatory65 drypowder compounds at dose in 01 DiI-HDL Cell Based Assay measuring activity
588392HTS 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_Set2confirmatory31 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 2
588403DiI Quencher Assay Measured in Biochemical System Using Plate Reader - 2085-08_Inhibitor_Dose_DryPowder_Activityconfirmatory31 drypowder compounds at dose in 08 DiI Quencher Assay measuring activity
588553HTS 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_Set3confirmatory32 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 3
588548HTS 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_Set4confirmatory32 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 4
588833HTS 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_Set7confirmatory588833#3 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 7
588829HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory17 drypowder compounds at dose in Cytotoxicity Assay in ldlA[SRB1] cells measuring activity set 2
588830HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-11_Inhibitor_Dose_DryPowder_Activityconfirmatory65 drypowder compounds at dose in 11 3 hour cytotoxicity assay measuring activity
588831HDL Inhib: Reversibility Measured in Cell-Based System Using Plate Reader - 2085-14_Inhibitor_Dose_DryPowder_Activityconfirmatory3 drypowder compounds at dose in 14 DiI-HDL Reversibility Assay measuring activity
602126HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set5confirmatory137 drypowder compounds at dose in Cytotoxicity Assay in ldlA[SRB1] cells measuring activity set 5
602134HDL Counter Assay: Tf Endo Assay Measured in Cell-Based System Using Plate Reader - 2085-04_Inhibitor_Dose_DryPowder_Activityconfirmatory13 drypowder compounds at dose in 04 Transferrin Endocytosis Assay measuring activity
602154HDL Inhib: Reversibility Measured in Cell-Based System Using Plate Reader - 2085-15_Inhibitor_Dose_DryPowder_Activityconfirmatory3 drypowder compounds at dose in 15 Extended reversibility DiI-HDL uptake Assay measuring activity
588836HDL Inhib: Activity in wild type cell line Measured in Cell-Based System Using Scintillation - 2085-12_Inhibitor_SinglePoint_DryPowder_Activityother5 drypowder compounds at singlepoint in 12 Radiolabeled HDL uptake in wild type SR-BI cells measuring activity
588837HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Scintillation - 2085-13_Inhibitor_SinglePoint_DryPowder_Activityother5 drypowder compounds at singlepoint in 13 Radiolabeled uptake of HDL in C384S mutant SR-BI cells measuring activity
588842HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set4confirmatory23 drypowder compounds at dose in Cytotoxicity Assay in ldlA[SRB1] cells measuring activity set 4
588843HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Plate Reader - 2085-10_Inhibitor_SinglePoint_DryPowder_Activityother31 drypowder compounds at singlepoint in 10 Cholesterol efflux assay with C384S Mutant measuring activity
602155Liposome Uptake Assay Measured in Biochemical System Using Scintillation - 2085-16_Inhibitor_Dose_DryPowder_Activityother4 drypowder compounds at dose in 16 Liposome Uptake Assay measuring activity
602152HDL MOA Assay: Efflux Assay Measured in Cell-Based System Using Plate Reader - 2085-06_Inhibitor_Dose_DryPowder_Activityother2 drypowder compounds at dose in 06 Cholesterol Efflux Assay measuring activity
602138HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Plate Reader - 2085-10_Inhibitor_Dose_DryPowder_Activityother2 drypowder compounds at dose in 10 Cholesterol efflux assay with C384S Mutant measuring activity
588754HTS 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_Set5confirmatory35 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 5
588818HDL MOA Assay: Efflux Assay Measured in Cell-Based System Using Plate Reader - 2085-06_Inhibitor_SinglePoint_DryPowder_Activityother5 drypowder compounds at singlepoint in 06 Cholesterol Efflux Assay measuring activity
588828HTS 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_Set6confirmatory17 drypowder compounds at dose in DiI-HDL Cell Based Assay measuring activity set 6
588826HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set3confirmatory37 drypowder compounds at dose in Cytotoxicity Assay in ldlA[SRB1] cells measuring activity set 3
588825HDL Uptake counterscreen Measured in Cell-Based System Using Plate Reader - 2085-07_Inhibitor_Dose_DryPowder_Activityconfirmatory17 drypowder compounds at dose in 07 HDL Uptake Activation Counterscreen measuring activity
588777HDL Orthogonal Assay: Alexa 488-HDL Measured in Cell-Based System Using Plate Reader - 2085-03_Inhibitor_Dose_DryPowder_Activityconfirmatory65 drypowder compounds at dose in 03 Alexa-488 labeled HDL Uptake Assay measuring activity
588810HDL Orthogonal Assay: Alexa 488-HDL Measured in Cell-Based System Using Plate Reader - 2085-03_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory35 drypowder compounds at dose in Alexa-488 labeled HDL Uptake Assay measuring activity set 2
624007HDL Uptake counterscreen Measured in Cell-Based System Using Plate Reader - 2085-07_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
624010HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Scintillation - 2085-13_Inhibitor_Dose_DryPowder_Activityconfirmatory
602285HTS 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_Set8confirmatory
624022HDL Inhib: Activity in wild type cell line Measured in Cell-Based System Using Scintillation - 2085-12_Inhibitor_Dose_DryPowder_Activityconfirmatory
624015HDL Inhib: Activity in mutant cell line Measured in Cell-Based System Using Plate Reader - 2085-10_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
624024HDL Orthogonal Assay: Alexa 488-HDL Measured in Cell-Based System Using Plate Reader - 2085-03_Inhibitor_Dose_DryPowder_Activity_Set3confirmatory
623895HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set6confirmatory
624017HDL MOA Assay: Efflux Assay Measured in Cell-Based System Using Plate Reader - 2085-06_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
623880HTS 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_Set9confirmatory
624026HDL Counter Assay: 3/24 Cytotox Measured in Cell-Based System Using Plate Reader - 2085-02_Inhibitor_Dose_DryPowder_Activity_Set7confirmatory
624029HTS 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_Set10confirmatory
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.
Additional Information
Grant Number: 2 R01 HL052212-11

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