Evidence map›Paper›PMID 29527168›Full record

ArticleFrontiers in pharmacology2018

Cefminox, a Dual Agonist of Prostacyclin Receptor and Peroxisome Proliferator-Activated Receptor-Gamma Identified by Virtual Screening, Has Therapeutic Efficacy against Hypoxia-Induced Pulmonary Hypertension in Rats.

Jingwen Xia, Li Yang, Liang Dong, Mengjie Niu, Shengli Zhang, Zhiwei Yang, Gulinuer Wumaier, Ying Li, Xiaomin Wei, Yi Gong and 2 more

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

Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 21 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

12 authors at 5 institutions in 1 country.

Jingwen XiaDepartment of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Li YangDepartment of Anesthesiology, Chongqing Medical University, Chongqing, China.
Liang DongDepartment of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Mengjie NiuDepartment of Gastroenterology Medicine, Xi'an Third Hospital, Xi'an, China.
Shengli ZhangDepartment of Applied Physics, Xi'an Jiaotong University, Xi'an, China.
Zhiwei YangDepartment of Applied Physics, Xi'an Jiaotong University, Xi'an, China.
Gulinuer WumaierDepartment of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Ying LiDepartment of Respiratory Medicine, Shaanxi Provincial Second People's Hospital, Xi'an, China.
Xiaomin WeiDepartment of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Yi GongDepartment of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Ning ZhuDepartment of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Shengqing LiDepartment of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Fudan University · CNHuashan Hospital · CNXi'an Jiaotong University · CNChongqing Medical University · CNXian Yang Central Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Prostacyclin receptor (IP) and peroxisome proliferator-activated receptor-gamma (PPARγ) are both potential targets for treatment of pulmonary arterial hypertension (PAH). Expression of IP and PPARγ decreases in PAH, suggesting that screening of dual agonists of IP and PPARγ might be an efficient method for drug discovery. Virtual screening (VS) of potential IP-PPARγ dual-targeting agonists was performed in the ZINC database. Ten of the identified compounds were further screened, and cefminox was found to dramatically inhibit growth of PASMCs with no obvious cytotoxicity. Growth inhibition by cefminox was partially reversed by both the IP antagonist RO113842 and the PPARγ antagonist GW9662. Investigation of the underlying mechanisms of action demonstrated that cefminox inhibits the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway through up-regulation of the expression of phosphatase and tensin homolog (PTEN, which is inhibited by GW9662), and enhances cyclic adenosine monophosphate (cAMP) production in PASMCs (which is inhibited by RO113842). In a rat model of hypoxia-induced pulmonary hypertension, cefminox displayed therapeutic efficacy not inferior to that of the prostacyclin analog iloprost or the PPARγ agonist rosiglitazone. Our results identified cefminox as a dual agonist of IP and PPARγ that significantly inhibits PASMC proliferation by up-regulation of PTEN and cAMP, suggesting that it has potential for treatment of PAH.

Indexed as

cyclic adenosine monophosphatehypoxia-induced pulmonary hypertensionperoxisome proliferator-activated receptor-gammaphosphatase and tensin homologprostacyclin receptor

Identifiers

PMID29527168
PMCPMC5829529
OpenAlexW2789873607

What OpenQuestion holds

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LicenceCC BY
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.