Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action.
Article in Bioorganic & medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
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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.
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5 · Who and what money
Authors and funding
3 authors.
Jonathan E HempelDivision of Cardiovascular Medicine, Vanderbilt University School of Medicine, 2220 Pierce Avenue, PRB 383, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, 896 Preston Research Building, Nashville, TN 37232, USA.
Adrian G CadarDivision of Cardiovascular Medicine, Vanderbilt University School of Medicine, 2220 Pierce Avenue, PRB 383, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall, Nashville, TN 37232, USA.
Charles C HongDivision of Cardiovascular Medicine, Vanderbilt University School of Medicine, 2220 Pierce Avenue, PRB 383, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, 896 Preston Research Building, Nashville, TN 37232, USA; Research Medicine, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA. Electronic address: charles.c.hong@vanderbilt.edu.
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI OWEN P MCGUINNESS · 2012 to 2026
$29.3M
TRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI MCGUINNESS, OWEN P · 1986 to 2011
$28.1M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 1989 to 2026
$19.6M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
Understanding and preventing HLA-associated drug reactionsP50GM115305 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DENNY, JOSHUA C. · 2015 to 2019
$13.0M
Vanderbilt/Meharry Initiative for Minority Student DvptR25GM062459 · NIGMS · VANDERBILT UNIVERSITY · PI VELEZ EDWARDS, DIGNA R · 2002 to 2020
$10.4M
Training In Cardiovascular ResearchT32HL007411 · NHLBI · VANDERBILT UNIVERSITY · PI BECKMAN, JOSHUA A · 1985 to 2020
$7.2M
Vanderbilt Mouse Metabolic Phenotyping CenterU2CDK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2016 to 2021
$6.3M
Cardiac Induction by Small Molecule BMP InhibitorsR01HL104040 · NHLBI · VANDERBILT UNIVERSITY · PI HONG, CHARLES C · 2010 to 2014
$2.0M
Chemical Genetic Analysis of Vertebrate DevelopmentR01GM118557 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HONG, CHARLES C · 2016 to 2019
From a high content in vivo screen for modulators of developmental patterning in embryonic zebrafish, we previously identified eggmanone (EGM1, 3) as a Hedgehog (Hh) signaling inhibitor functioning downstream of Smoothened. Phenotypic optimization studies for in vitro probe development utilizing a Gli transcription-linked stable luciferase reporter cell line identified EGM1 analogs with improved potency and aqueous solubility. Mechanistic profiling of optimized analogs indicated two distinct scaffold clusters: PDE4 inhibitors able to inhibit downstream of Sufu, and PDE4-independent Hh inhibitors functioning between Smo and Sufu. Each class represents valuable in vitro probes for elucidating the complex mechanisms of Hh regulation.
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 OpenQuestion graph.
Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action. · full record | OpenQuestion