Evidence map›Paper›PMID 29890824›Full record

ArticleMolecules and cells2018

Crystal Structures of Spleen Tyrosine Kinase in Complex with Two Novel 4-Aminopyrido[4,3-d] Pyrimidine Derivative Inhibitors.

Sang Jae Lee, Jang-Sik Choi, Seoung Min Bong, Hae-Jun Hwang, Jaesang Lee, Ho-Juhn Song, Jaekyoo Lee, Jung-Ho Kim, Jong Sung Koh, Byung Il Lee

Open access · greenAbstract read
In one paragraph

Article in Molecules and cells, 2018. 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
0.2field-weighted citation impact, top 44% 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, 2 citations in OpenAlex.

  1. 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

10 authors at 2 institutions in 1 country.

Sang Jae LeeResearch Institute, National Cancer Center, Goyang, Gyeonggi 10408, Korea.
Jang-Sik ChoiOscotec Inc., Seongnam 13488, Korea.
Seoung Min BongResearch Institute, National Cancer Center, Goyang, Gyeonggi 10408, Korea.
Hae-Jun HwangOscotec Inc., Seongnam 13488, Korea.
Jaesang LeeOscotec Inc., Seongnam 13488, Korea.
Ho-Juhn SongGenosco, 767C Concord Ave, 2nd Floor, Cambridge, MA 02138, USA.
Jaekyoo LeeGenosco, 767C Concord Ave, 2nd Floor, Cambridge, MA 02138, USA.
Jung-Ho KimOscotec Inc., Seongnam 13488, Korea.
Jong Sung KohGenosco, 767C Concord Ave, 2nd Floor, Cambridge, MA 02138, USA.
Byung Il LeeResearch Institute, National Cancer Center, Goyang, Gyeonggi 10408, Korea.
National Cancer Center · KRSeoul National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spleen tyrosine kinase (SYK) is a cytosolic non-receptor protein tyrosine kinase. Because SYK mediates key receptor signaling pathways involving the B cell receptor and Fc receptors, SYK is an attractive target for autoimmune disease and cancer treatments. To date, representative oral SYK inhibitors, including fostamatinib (R406 or R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659, have been assessed in clinical trials. Here, we report the crystal structures of SYK in complex with two newly developed inhibitors possessing 4-aminopyrido[4,3-D]pyrimidine moieties (SKI-G-618 and SKI-O-85). One SYK inhibitor (SKI-G-618) exhibited moderate inhibitory activity against SYK, whereas the other inhibitor (SKI-O-85) exhibited a low inhibitory profile against SYK. Binding mode analysis indicates that a highly potent SYK inhibitor might be developed by modifying and optimizing the functional groups that interact with Leu377, Gly378, and Val385 in the G-loop and the nearby region in SYK. In agreement with our structural analysis, one of our SYK inhibitor (SKI-G-618) shows strong inhibitory activities on the

Indexed as

HumansPhosphorylationProtein Kinase InhibitorsSignal TransductionSyk KinaseProtein Kinase InhibitorsSyk KinaseSYK protein, humancancercrystal structurerheumatoid arthritisspleen tyrosine kinaseSYK

Identifiers

PMID29890824
PMCPMC6030240
OpenAlexW2811406019

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.