Evidence map›Paper›PMID 24900830›Full record

ArticleACS medicinal chemistry letters2014

Discovery and Biological Evaluation of Novel Dual EGFR/c-Met Inhibitors.

Bálint Szokol, Pál Gyulavári, Ibolya Kurkó, Ferenc Baska, Csaba Szántai-Kis, Zoltán Greff, Zoltán Orfi, István Peták, Kinga Pénzes, Robert Torka and 4 more

Abstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
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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

14 authors.

Bálint SzokolVichem Chemie Research Ltd. , 1022 Budapest, Hungary.
Pál GyulaváriMTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University , 1085 Budapest, Hungary.
Ibolya KurkóVichem Chemie Research Ltd. , 1022 Budapest, Hungary.
Ferenc BaskaVichem Chemie Research Ltd. , 1022 Budapest, Hungary ; Rational Drug-Design Laboratory Cooperation Research Centre, Semmelweis University , 1085 Budapest, Hungary.
Csaba Szántai-KisVichem Chemie Research Ltd. , 1022 Budapest, Hungary.
Zoltán GreffVichem Chemie Research Ltd. , 1022 Budapest, Hungary.
Zoltán OrfiRational Drug-Design Laboratory Cooperation Research Centre, Semmelweis University , 1085 Budapest, Hungary ; Max Planck Institute of Biochemistry , Munich 82152, Germany.
István PetákMTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University , 1085 Budapest, Hungary ; KPS Medical Biotechnology and Healthcare Services Ltd. , 1022 Budapest, Hungary.
Kinga PénzesMax Planck Institute of Biochemistry , Munich 82152, Germany.
Robert TorkaMax Planck Institute of Biochemistry , Munich 82152, Germany.
Axel UllrichMax Planck Institute of Biochemistry , Munich 82152, Germany.
László OrfiVichem Chemie Research Ltd. , 1022 Budapest, Hungary ; Department of Pharmaceutical Chemistry, Semmelweis University , 1085 Budapest, Hungary.
Tibor VántusMTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University , 1085 Budapest, Hungary.
György KériVichem Chemie Research Ltd. , 1022 Budapest, Hungary ; MTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University , 1085 Budapest, Hungary ; Rational Drug-Design Laboratory Cooperation Research Centre, Semmelweis University , 1085 Budapest, Hungary.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Activating mutations in the epidermal growth factor receptor (EGFR) have been identified in a subset of non-small cell lung cancer (NSCLC), which is one of the leading cancer types worldwide. Application of EGFR tyrosine kinase inhibitors leads to acquired resistance by secondary EGFR mutations or by amplification of the hepatocyte growth factor receptor (c-Met) gene. Although several EGFR and c-Met inhibitors have been reported, potent dual EGFR/c-Met inhibitors, which can overcome this latter resistance mechanism, have hitherto not been published and have not reached clinical trials. In the present study we have identified dual EGFR/c-Met inhibitors and designed novel N-[4-(quinolin-4-yloxy)-phenyl]-biarylsulfonamide derivatives, which inhibit the c-Met receptor and both the wild-type and the activating mutant EGFR kinases in nanomolar range. We have demonstrated by Western blot analysis that compound 10 inhibits EGFR and c-Met phosphorylation at cellular level and effectively inhibits viability of the NSCLC cell lines.

Indexed as

acquired resistancec-MetEGFRkinase inhibitorNSCLC

Identifiers

PMID24900830
PMCPMC4027597

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.