Evidence map›Paper›PMID 34676038›Full record

ArticleACS medicinal chemistry letters2021

Rational Design, Optimization, and Biological Evaluation of Novel MEK4 Inhibitors against Pancreatic Adenocarcinoma.

Ada J Kwong, Thao N D Pham, Hannah E Oelschlager, Hidayatullah G Munshi, Karl A Scheidt

Open access · greenAbstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Refinement of MEK inhibitors.Future medicinal chemistry · 2025
    Article
  4. Article
  5. MKK4 Inhibitors-Recent Development Status and Therapeutic Potential.International journal of molecular sciences · 2023
    Review
  6. GZ17-6.02 kills prostate cancer cellsFrontiers in oncology · 2022
    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

5 authors at 1 institution in 1 country.

Ada J KwongDepartment of Chemistry, Department of Pharmacology, Feinberg School of Medicine, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.ORCID https://orcid.org/0000-0003-2608-7442
Thao N D PhamDepartment of Medicine, Feinberg School of Medicine, Northwestern University, 303 E. Superior Street, Chicago, Illinois 60611, United States.
Hannah E OelschlagerDepartment of Chemistry, Department of Pharmacology, Feinberg School of Medicine, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.
Hidayatullah G MunshiDepartment of Medicine, Feinberg School of Medicine, Northwestern University, 303 E. Superior Street, Chicago, Illinois 60611, United States.
Karl A ScheidtDepartment of Chemistry, Department of Pharmacology, Feinberg School of Medicine, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.ORCID https://orcid.org/0000-0003-4856-3569
Northwestern University · US

Funding

Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
TRAINING PROGRAM IN SIGNAL TRANSDUCTION AND CANCERT32CA070085 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1997 to 2026
$5.7M
Chemistry of Life Processes Predoctoral Training ProgramT32GM105538 · NIGMS · NORTHWESTERN UNIVERSITY · PI KELLEHER, NEIL L · 2013 to 2022
$2.7M
Galpha13 and pancreatic cancer progressionR01CA217907 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MUNSHI, HIDAYATULLAH G. · 2018 to 2022
$1.8M
Echo Acoustic Liquid Handler for High Throughput Analysis LabS10OD023681 · OD · NORTHWESTERN UNIVERSITY · PI WEISS, ERIC LYLE · 2018 to 2018
$550k
Rapid evaluation of immunotherapy regimens in ex vivo human pancreatic tumor slice cultures.R21CA255291 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MUNSHI, HIDAYATULLAH G. · 2021 to 2022
$406k
Synthesis, and Evaluation of Potent and Selective MEK4 Inhibitors as a Targeted Therapeutic for Metastatic Pancreatic Ductal AdenocarcinomaF31CA250353 · NCI · NORTHWESTERN UNIVERSITY · PI KWONG, ADA JADE · 2020 to 2021
$75k
NCATS NIH HHS UL1 TR001422NCI NIH HHS F31 CA250353NCI NIH HHS R01 CA217907NCI NIH HHS R21 CA255291NCI NIH HHS T32 CA070085NIGMS NIH HHS T32 GM105538NIH HHS S10 OD023681
6 · The paper itself

Abstract

Growth, division, and development of healthy cells relies on efficient response to environmental survival cues. The conserved mitogen-activated protein kinase (MAPK) family of pathways interface extracellular stimuli to intracellular processes for this purpose. Within these pathways, the MEK family has been identified as a target of interest due to its clinical relevance. Particularly, MEK4 has drawn recent attention for its indications in pancreatic and prostate cancers. Here, we report two potent MEK4 inhibitors demonstrating significant reduction of phospho-JNK and antiproliferative properties against pancreatic cancer cell lines. Furthermore, molecular inhibition of MEK4 pathway activates the MEK1/2 pathway, with the combination of MEK1/2 and MEK4 inhibitors demonstrating synergistic effects against pancreatic cancer cells. Our inhibitors provided insight into the crosstalk between MAPK pathways and new tools for elucidating the roles of MEK4 in disease states, findings which will pave the way for better understanding of the MAPK pathways and development of additional probes.

Identifiers

PMID34676038
PMCPMC8521629
OpenAlexW3200647610

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.