Evidence map›Paper›PMID 28360334›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2017

A Genomic DNA Reporter Screen Identifies Squalene Synthase Inhibitors That Act Cooperatively with Statins to Upregulate the Low-Density Lipoprotein Receptor.

Alastair G Kerr, Lawrence C S Tam, Ashley B Hale, Milena Cioroch, Gillian Douglas, Sarina Agkatsev, Olivia Hibbitt, Joseph Mason, James Holt-Martyn, Carole J R Bataille and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Alastair G KerrDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Lawrence C S TamDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Ashley B HaleDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Milena CiorochDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Gillian DouglasDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Sarina AgkatsevDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Olivia HibbittDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Joseph MasonDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
James Holt-MartynDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Carole J R BatailleDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Graham M WynneDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Keith M ChannonDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Angela J RussellDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.).
Richard Wade-MartinsDepartments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom (J.M., C.J.R.B., G.M.W., A.J.R.) richard.wade-martins@dpag.ox.ac.uk angela.russell@chem.ox.ac.uk.
British Heart Foundation · GBUniversity of Oxford · GBJohn Radcliffe Hospital · GB

Funding

British Heart Foundation PG/10/54/28460British Heart Foundation RG/17/10/32859Medical Research Council G0400144
6 · The paper itself

Abstract

Hypercholesterolemia remains one of the leading risk factors for the development of cardiovascular disease. Many large double-blind studies have demonstrated that lowering low-density lipoprotein (LDL) cholesterol using a statin can reduce the risk of having a cardiovascular event by approximately 30%. However, despite the success of statins, some patient populations are unable to lower their LDL cholesterol to meet the targeted lipid levels, due to compliance or potency issues. This is especially true for patients with heterozygous familial hypercholesterolemia who may require additional upregulation of the low-density lipoprotein receptor (LDLR) to reduce LDL cholesterol levels below those achievable with maximal dosing of statins. Here we identify a series of small molecules from a genomic DNA reporter screen that upregulate the LDLR in mouse and human liver cell lines at nanomolar potencies (EC

Indexed as

AnimalsCell Line, TumorCHO CellsCricetinaeCricetulusDose-Response Relationship, DrugDrug SynergismEnzyme InhibitorsFarnesyl-Diphosphate FarnesyltransferaseGenetic TestingHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMiceReceptors, LDLSmall Molecule LibrariesEnzyme InhibitorsFarnesyl-Diphosphate FarnesyltransferaseHydroxymethylglutaryl-CoA Reductase InhibitorsLDLR protein, humanReceptors, LDLSmall Molecule Libraries

Identifiers

PMID28360334
PMCPMC5443320
OpenAlexW2603144437

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.