Evidence map›Paper›PMID 31045568›Full record

ArticleActa crystallographica. Section F, Structural biology communications2019

Evaluation of a crystallographic surrogate for kallikrein 5 in the discovery of novel inhibitors for Netherton syndrome.

James H Thorpe, Emma V Edgar, Kathrine J Smith, Xiao Q Lewell, Monika Rella, Gemma V White, Oxana Polyakova, Pamela Nassau, Ann L Walker, Duncan S Holmes and 4 more

Open access · greenAbstract read
In one paragraph

Article in Acta crystallographica. Section F, Structural biology communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 34% 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

1 citing paper in PubMed, 7 citations in OpenAlex.

  1. Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025
    Review
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 2 countries.

James H ThorpeGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Emma V EdgarGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Kathrine J SmithGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Xiao Q LewellGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Monika RellaGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Gemma V WhiteGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Oxana PolyakovaGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Pamela NassauGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Ann L WalkerGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Duncan S HolmesGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Andrew C PearceGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Yichen WangINSERM UMR1163 Laboratory of Genetic Skin Diseases, Imagine Institute and Université Paris Descartes-Sorbonne Paris Cité, Paris, France.
John LiddleGlaxoSmithKline, Medicinal Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, England.
Alain HovnanianINSERM UMR1163 Laboratory of Genetic Skin Diseases, Imagine Institute and Université Paris Descartes-Sorbonne Paris Cité, Paris, France.
GlaxoSmithKline (India) · INInstitut des Maladies Génétiques Imagine · FRSorbonne Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The inhibition of kallikrein 5 (KLK5) has been identified as a potential strategy for treatment of the genetic skin disorder Netherton syndrome, in which loss-of-function mutations in the SPINK5 gene lead to down-regulation of the endogenous inhibitor LEKTI-1 and profound skin-barrier defects with severe allergic manifestations. To aid in the development of a medicine for this target, an X-ray crystallographic system was developed to facilitate fragment-guided chemistry and knowledge-based drug-discovery approaches. Here, the development of a surrogate crystallographic system in place of KLK5, which proved to be challenging to crystallize, is described. The biochemical robustness of the crystallographic surrogate and the suitability of the system for the study of small nonpeptidic fragments and lead-like molecules are demonstrated.

Indexed as

Amino Acid SequenceAnimalsBaculoviridaeBenzamidinesBinding SitesCloning, MolecularCrystallography, X-RayDrug DiscoveryGene ExpressionGenetic VectorsHumansKallikreinsKineticsModels, MolecularMutationNetherton SyndromeBenzamidinesKallikreinsKLK5 protein, humanKLK6 protein, humanProtease InhibitorsRecombinant ProteinsGSK144kallikreinmedicinal chemistryNetherton syndromestructure-guided design

Identifiers

PMID31045568
PMCPMC6497096
OpenAlexW2941570618

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.