Evidence map›Paper›PMID 26094120›Full record

ArticleBioorganic & medicinal chemistry letters2015

Small molecule inhibits activity of scavenger receptor A: Lead identification and preliminary studies.

Yunyun Yuan, Xia Li, Saheem A Zaidi, Christopher K Arnatt, Xiaofei Yu, Chunqing Guo, Xiang-Yang Wang, Yan Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

5 citing papers in PubMed, 13 citations in OpenAlex.

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  5. Review
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

8 authors at 1 institution in 1 country.

Yunyun YuanDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
Xia LiDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Saheem A ZaidiDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
Christopher K ArnattDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
Xiaofei YuDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Chunqing GuoDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Xiang-Yang WangDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: xywang@vcu.edu.
Yan ZhangDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA. Electronic address: yzhang2@vcu.edu.
Virginia Commonwealth University · US

Funding

Host-tumor interactions and cancer relapse after radiation therapyR01CA175033 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI WANG, XIANG-YANG SHAWN · 2014 to 2018
$1.6M
Large Stress Proteins in Biology and MedicineR01CA154708 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI WANG, XIANG-YANG SHAWN · 2011 to 2015
$1.5M
Scavenger Receptor-A and Immune RegulationR01CA129111 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI WANG, XIANG-YANG SHAWN · 2007 to 2011
$1.2M
NCI NIH HHS CA175033NCI NIH HHS R01 CA129111NCI NIH HHS R01 CA154708NCI NIH HHS R01 CA175033
6 · The paper itself

Abstract

Scavenger receptor A (SRA) has been implicated in the processes of tumor invasion and acts as an immunosuppressor during therapeutic cancer vaccination. Pharmacological inhibition of SRA function thus holds a great potential to improve treatment outcome of cancer therapy. Macromolecular natural product sennoside B was recently shown to block SRA function. Here we report the identification and characterization of a small molecule SRA inhibitor rhein. Rhein, a deconstructed analog of sennoside B, reversed the suppressive activity of SRA in dendritic cell-primed T cell activation, indicated by transcription activation of il2 gene and production of IL-2. Rhein also inhibited SRA ligand polyinosinic:polycytidylic acid (poly(I:C)) induced activation of transcriptional factors, including interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 1 (STAT1). Additionally, this newly identified lead compound was docked into the homology models of the SRA cysteine rich domain to gain insights into its interaction with the receptor. It was then found that rhein can favorably interact with SRA cysteine rich domain. Collectively, rhein, being the first identified small molecule inhibitors for SRA, warrants further structure-activity relationship studies, which may lead to development of novel pharmacological intervention for cancer therapy.

Indexed as

AnimalsAnthraquinonesAntineoplastic Agentsbeta-GalactosidaseDendritic CellsDrug DesignHumansInterferon Regulatory Factor-3Lymphocyte ActivationMice, Inbred C57BLMice, KnockoutModels, MolecularPoly I-CScavenger Receptors, Class ASenna ExtractSennosidesAnthraquinonesAntineoplastic Agentsbeta-GalactosidaseInterferon Regulatory Factor-3IRF3 protein, humanPoly I-CrheinScavenger Receptors, Class ASenna ExtractSennosidesSmall Molecule LibrariesToll-Like ReceptorsTranscription FactorsCancer therapyCysteine-rich domainHomology modelNatural productRheinScavenger receptor A

Identifiers

PMID26094120
PMCPMC4494979
OpenAlexW615300668

What OpenQuestion holds

Textmetadata
LicenceTDM
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.