Evidence map›Paper›PMID 34491744›Full record

ArticleJournal of medicinal chemistry2021

Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors.

Li Liu, Manshu Tang, Rajan Pragani, Frank G Whitby, Ya-Qin Zhang, Bijina Balakrishnan, Yuhong Fang, Surendra Karavadhi, Dingyin Tao, Christopher A LeClair and 7 more

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2021. 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
–field-weighted citation impact
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.

  1. Article
  2. Article
  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

17 authors.

Li LiuNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
Manshu TangDepartment of Pediatrics, University of Utah, Salt Lake City, Utah 84108-6500, United States.
Rajan PraganiNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
Frank G WhitbyDepartment of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Salt Lake City, Utah 84112, United States.
Ya-Qin ZhangNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
Bijina BalakrishnanDepartment of Pediatrics, University of Utah, Salt Lake City, Utah 84108-6500, United States.
Yuhong FangNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
Surendra KaravadhiNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
Dingyin TaoNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.ORCID 0000-0001-6531-2740
Christopher A LeClairNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.ORCID 0000-0002-2746-5938
Matthew D HallNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.ORCID 0000-0002-5073-442X
Juan J MaruganNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.ORCID 0000-0002-3951-7061
Matthew BoxerNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
Min ShenNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.
Christopher P HillDepartment of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Salt Lake City, Utah 84112, United States.
Kent LaiDepartment of Pediatrics, University of Utah, Salt Lake City, Utah 84108-6500, United States.
Samarjit PatnaikNational Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.ORCID 0000-0002-4265-7620

Funding

X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Towards Improved Therapy for Classic GalactosemiaR01HD089933 · NICHD · UNIVERSITY OF UTAH · PI LAI, KENT · 2017 to 2019
$948k
Toward Improved Therapy for Classic GalactosemiaR03MH085689 · NIMH · UNIVERSITY OF UTAH · PI LAI, KENT · 2008 to 2008
$24k
NICHD NIH HHS R01 HD089933NIGMS NIH HHS P41 GM103393NIMH NIH HHS R03 MH085689
6 · The paper itself

Abstract

Classic galactosemia is a rare disease caused by inherited deficiency of galactose-1 phosphate uridylyltransferase (GALT). Accumulation of galactose-1 phosphate (gal-1P) is thought to be the major cause of the chronic complications associated with this disease, which currently has no treatment. Inhibiting galactokinase (GALK1), the enzyme that generates galactose-1 phosphate, has been proposed as a novel strategy for treating classic galactosemia. Our previous work identified a highly selective unique dihydropyrimidine inhibitor against GALK1. With the determination of a co-crystal structure of this inhibitor with human GALK1, we initiated a structure-based structure-activity relationship (SAR) optimization campaign that yielded novel analogs with potent biochemical inhibition (IC

Indexed as

AnimalsCrystallography, X-RayEnzyme InhibitorsFemaleGalactokinaseHumansMaleMiceMolecular StructureProtein BindingPyrimidinesStructure-Activity RelationshipEnzyme InhibitorsGalactokinasePyrimidines

Identifiers

PMID34491744
PMCPMC8884033

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.