Evidence map›Paper›PMID 36043792›Full record

ArticleCombinatorial chemistry & high throughput screening2023

Small-molecule High-throughput Screening Identifies an MEK Inhibitor PD198306 that Enhances Sorafenib Efficacy via MCL-1 and BIM in Hepatocellular Carcinoma Cells.

Junjie Hong, Wei Zheng, Xiujun Cai

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

Article in Combinatorial chemistry & high throughput screening, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
0.1field-weighted citation impact, top 52% 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, 1 synthesis or guideline pooled it, 1 citations in OpenAlex.

  1. Pooled it
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

3 authors at 3 institutions in 2 countries.

Junjie HongDepartment of General Surgery, Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310016, China.
Wei ZhengNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Xiujun CaiDepartment of General Surgery, Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310016, China.
National Center for Advancing Translational Sciences · USNational Institutes of Health · USZhejiang University · CN

Funding

Drug Repurposing Screening for Rare and Neglected DiseasesZIATR000018 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI ZHENG, WEI · 2015 to 2025
$24.6M
Intramural NIH HHS ZIA TR000018
6 · The paper itself

Abstract

backgroundSorafenib is the most widely used systematic therapy drug for treating unresectable Hepatocellular Carcinoma (HCC) but showed dissatisfactory efficacy in clinical applications.

objectiveWe conducted a combinational quantitative small-molecule high-throughput screening (qHTS) to identify potential candidates to enhance the treatment effectiveness of sorafenib.

methodsFirst, using a Hep3B human HCC cell line, 7051 approved drugs and bioactive compounds were screened, then the primary hits were tested with/without 0.5 μM sorafenib respectively, the compound has the half maximal Inhibitory Concentration (IC50) shift value greater than 1.5 was thought to have the synergistic effect with sorafenib. Furthermore, the MEK inhibitor PD198306 was selected for the further mechanistic study.

results12 effective compounds were identified, including kinase inhibitors targeting MEK, AURKB, CAMK, ROCK2, BRAF, PI3K, AKT and EGFR, and a μ-opioid receptor agonist and a Ltype calcium channel blocker. The mechanistic research of the combination of sorafenib plus PD198306 showed that the two compounds synergistically inhibited MEK-ERK and mTORC1- 4EBP1 and induced apoptosis in HCC cells, which can be attributed to the transcriptional and posttranslational regulation of MCL-1 and BIM.

conclusionSmall-molecule qHTS identifies MEK inhibitor PD1938306 as a potent sorafenib enhancer, together with several novel combination strategies that are valuable for further studies.

Indexed as

Antineoplastic AgentsCarcinoma, HepatocellularLiver NeoplasmsApoptosisBcl-2-Like Protein 11Cell Line, TumorCell ProliferationFluorobenzenesHigh-Throughput Screening AssaysHumansMitogen-Activated Protein Kinase KinasesMyeloid Cell Leukemia Sequence 1 ProteinProtein Kinase InhibitorsSorafenibAntineoplastic AgentsBcl-2-Like Protein 11FluorobenzenesMitogen-Activated Protein Kinase KinasesMyeloid Cell Leukemia Sequence 1 ProteinPD 198306Protein Kinase InhibitorsSorafenibangiogenesiscalcium channel blockerhepatocellular carcinomaMEK inhibitorSmall-molecule high-throughput screeningsorafenib

Identifiers

PMID36043792
PMCPMC9971357
OpenAlexW4293560591

What Socratic 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 Socratic graph.