Evidence map›Paper›PMID 25124115›Full record

ArticleBioorganic & medicinal chemistry letters2014

Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1.

Yalda Bravo, Peter Teriete, Raveendra-Panickar Dhanya, Russell Dahl, Pooi San Lee, Tina Kiffer-Moreira, Santhi Reddy Ganji, Eduard Sergienko, Layton H Smith, Colin Farquharson and 2 more

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

Article in Bioorganic & medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  3. Review
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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

12 authors at 3 institutions in 2 countries.

Yalda BravoCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Peter TerieteCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Raveendra-Panickar DhanyaCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Russell DahlCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Pooi San LeeCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Tina Kiffer-MoreiraSanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Santhi Reddy GanjiCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Eduard SergienkoConrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Layton H SmithConrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Colin FarquharsonThe Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, Scotland, UK.
José Luis MillánSanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nicholas D P CosfordCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: ncosford@sanfordburnham.org.
Sanford Burnham Prebys Medical Discovery Institute · USDiscovery Institute · USUniversity of Edinburgh · GB

Funding

Sanford-Burnham Center for Chemical GenomicsU54HG005033 · NHGRI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI JACKSON, MICHAEL · 2008 to 2012
$72.5M
Mechanisms of initiation of skeletal mineralizationR01AR053102 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 2006 to 2015
$3.8M
Lead Optimization of Novel Inhibitors of Tissue Non-specific Alkaline PhosphataseR01AG045933 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI COSFORD, NICHOLAS DAVID, MILLAN, JOSE LUIS · 2013 to 2015
$2.2M
Leads and Target Validation for Vascular Calcification in Chronic Kidney DiseaseRC1HL101899 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 2009 to 2010
$977k
Biotechnology and Biological Sciences Research Council BBS/E/R/00003741NHGRI NIH HHS HG005033NHGRI NIH HHS U54 HG005033NHLBI NIH HHS RC1 HL101899NHLBI NIH HHS RC1HL10899NIAMS NIH HHS AR53102NIAMS NIH HHS R01 AR053102NIA NIH HHS R01 AG045933
6 · The paper itself

Abstract

We report the discovery and characterization of a series of benzoisothiazolone inhibitors of PHOSPHO1, a newly identified soluble phosphatase implicated in skeletal mineralization and soft tissue ossification abnormalities. High-throughput screening (HTS) of a small molecule library led to the identification of benzoisothiazolones as potent and selective inhibitors of PHOSPHO1. Critical structural requirements for activity were determined, and the compounds were subsequently derivatized and measured for in vitro activity and ADME parameters including metabolic stability and permeability. On the basis of its overall profile the benzoisothiazolone analogue 2q was selected as MLPCN probe ML086.

Indexed as

Drug DesignAnimalsBenzamidesBenzothiazolesDose-Response Relationship, DrugEnzyme InhibitorsHepatocytesHigh-Throughput Screening AssaysHumansHydrogen-Ion ConcentrationMiceMolecular StructurePhosphoric Monoester HydrolasesSmall Molecule LibrariesStructure-Activity RelationshipBenzamidesBenzothiazolesEnzyme InhibitorsML086 compoundPHOSPHO1 protein, humanPhosphoric Monoester HydrolasesSmall Molecule LibrariesML086PhosphatasePHOSPHO1Probe compoundVascular calcification

Identifiers

PMID25124115
PMCPMC4170737
OpenAlexW2057630755

What OpenQuestion holds

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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 OpenQuestion graph.