Evidence map›Paper›PMID 31391482›Full record

ArticleScientific reports2019

A protein scaffold, engineered SPINK2, for generation of inhibitors with high affinity and specificity against target proteases.

Daisuke Nishimiya, Yoshirou Kawaguchi, Shiho Kodama, Hatsumi Nasu, Hidenori Yano, Aya Yamaguchi, Masakazu Tamura, Ryuji Hashimoto

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. 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

8 authors.

Daisuke NishimiyaDAIICHI SANKYO CO., LTD., Biologics Division, Modality Research Laboratories, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan. nishimiya.daisuke.tc@daiichisankyo.co.jp.
Yoshirou KawaguchiDAIICHI SANKYO CO., LTD., Biologics Division, Modality Research Laboratories, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
Shiho KodamaDAIICHI SANKYO CO., LTD., Biologics Division, Modality Research Laboratories, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
Hatsumi NasuDAIICHI SANKYO CO., LTD., Biologics Division, Modality Research Laboratories, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
Hidenori YanoDAIICHI SANKYO CO., LTD., Biologics Division, Modality Research Laboratories, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
Aya YamaguchiDAIICHI SANKYO CO., LTD., Biologics Division, Modality Research Laboratories, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
Masakazu TamuraDAIICHI SANKYO CO., LTD., Biologics Division, Modality Research Laboratories, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
Ryuji HashimotoDAIICHI SANKYO CO., LTD., Biologics Division, Modality Research Laboratories, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteases are one of attractive therapeutic targets to play key roles in pharmacological action. There are many protease inhibitors in nature, and most of them structurally have cystine knot motifs. Their structures are favorable for recognition of active pockets of proteases, leading to the potent inhibition. However, they also have drawbacks, such as broad cross-reactivity, on the therapeutic application. To create therapeutic proteins derived from a disulfide-rich scaffold, we selected human serine protease inhibitor Kazal type 2 (SPINK2) through a scaffold screening, as a protein scaffold with requirements for therapeutic proteins. We then constructed a diverse library of the engineered SPINK2 by introducing random mutations into its flexible loop region with the designed method. By phage panning against four serine proteases, we isolated potent inhibitors against each target with picomolar K

Indexed as

Drug DesignMutagenesisCrystallography, X-RayGlycoproteinsKallikreinsModels, MolecularProtein EngineeringProtein Structure, TertiarySerine Peptidase Inhibitors, Kazal TypeSerine ProteasesSerine Proteinase InhibitorsStructure-Activity RelationshipGlycoproteinskallikrein 4KallikreinsSerine Peptidase Inhibitors, Kazal TypeSerine ProteasesSerine Proteinase InhibitorsSPINK2 protein, human

Identifiers

PMID31391482
PMCPMC6686015

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Registered trials

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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.