Evidence map›Paper›PMID 33777680›Full record

ArticleActa pharmaceutica Sinica. B2021

A multifunctional cross-validation high-throughput screening protocol enabling the discovery of new SHP2 inhibitors.

Yihui Song, Min Zhao, Yahong Wu, Bin Yu, Hong-Min Liu

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

Article in Acta pharmaceutica Sinica. B, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.8field-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

15 citing papers in PubMed, 33 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Yihui SongSchool of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China.
Min ZhaoSchool of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China.
Yahong WuSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
Bin YuSchool of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China.
Hong-Min LiuSchool of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China.
Zhengzhou University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Of note, this protocol showed potential for identifying SHP2 inhibitors against cancer-associated SHP2 mutation SHP2-E76A. After initial screening of our in-house compound library (∼2300 compounds), we identified 4 new SHP2-PTP inhibitors (0.17% hit rate) and 28 novel allosteric SHP2 inhibitors (1.22% hit rate), of which SYK-85 and WS-635 effectively inhibited SHP2-PTP (SYK-85: IC

Indexed as

AKT, protein kinase BALK, anaplastic lymphoma kinaseAllosteric inhibitorsAML, acute myelogenous leukemiaBis-tris, bis-(2-hydroxyethyl)amino-tris(hydroxymethyl)methaneBTLA, B and T lymphocyte attenuatorDiFMU, 6,8-difluoro-4-methylumbelliferyl hydroxidDiFMUP, 6,8-difluoro-4-methylumbelliferyl phosphateDTT, dithiothreitolEnzyme assayFI, fluorescence intensityHEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidHigh-throughput screeningHTS, high-throughput screeningIC50, half maximal inhibitory concentrationJAK, janus kinaseJMML, juvenile myelomonocytic leukaemiaLB, lysogeny brothLOC, ligand only controlLS, LEOPARD syndromeMAPK, mitogen-activated protein kinaseMEK, extracellular regulated protein kinase kinasesNPC, no protein controlNS, Noonan syndromeOD, optical densityPD-1, programmed death 1PI3K, phosphatidylinositol 3 kinasep-IRS1, phosphorylated insulin receptor substrate 1PMSF, phenylmethanesulfonyl fluoridePTP, protein tyrosine phosphataseR2, coefficient of determinationRAS, rat sarcomaS/B, signal over backgroundSDS-PAGE, sodium dodecyl sulphate polyacyrlamide gel electrophoresisSD, standard deviationSH2, Src homology 2SHP2SHP2-PTP, protein tyrosine phosphatase domain of Src homology phosphotyrosyl phosphatase 2SHP2, Src homology phosphotyrosyl phosphatase 2SHP2-WT, wild type Src homology phosphotyrosyl phosphatase 2STAT, signal transducer and activator of transcriptionThermal shift assayTm, melting temperatureΔTm, melting temperature change

Identifiers

PMID33777680
PMCPMC7982506
OpenAlexW3095280134

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.