Evidence map›Paper›PMID 30981691›Full record

ArticleEuropean journal of medicinal chemistry2019

Development of CXCR4 modulators based on the lead compound RB-108.

Renren Bai, Xiaokang Jie, Jian Sun, Zhongxing Liang, Younghyoun Yoon, Amber Feng, Yoonhyeun Oum, Wenyan Yu, Rui Wu, Bin Sun and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medicinal chemistry, 2019. 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. Review
  2. Review
  3. A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  4. CXCL12 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021
    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

13 authors.

Renren BaiCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China. Electronic address: renrenbai@zjut.edu.cn.
Xiaokang JieCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Jian SunCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Zhongxing LiangDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Younghyoun YoonDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Amber FengDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Yoonhyeun OumDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Wenyan YuCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Rui WuCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Bin SunKey Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Zhejiang University of Technology, Hangzhou, China.
Eric SalgadoDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Yuanyuan XieCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China; Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Zhejiang University of Technology, Hangzhou, China.
Hyunsuk ShimDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute, Emory University, Atlanta, GA, USA. Electronic address: hshim@emory.edu.

Funding

Graduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1M
Development of anti-CXCR4 compounds to block breast cancer metastasisR01CA165306 · NCI · EMORY UNIVERSITY · PI SHIM, HYUNSUK · 2012 to 2016
$1.7M
NCI NIH HHS R01 CA165306NIGMS NIH HHS T32 GM008602
6 · The paper itself

Abstract

The CXCR4/CXCL12 axis plays prominent roles in tumor metastasis and inflammation. CXCR4 has been shown to be involved in a variety of inflammation-related diseases. Therefore, CXCR4 is a promising potential target to develop novel anti-inflammatory agents. Taking our previously discovered CXCR4 modulator RB-108 as the lead compound, a series of derivatives were synthesized structurally modifying and optimizing the amide and sulfamide side chains. The derivatives successfully maintained potent CXCR4 binding affinity. Furthermore, compounds IIb, IIc, IIIg, IIIj, and IIIm were all efficacious in inhibiting the invasion of CXCR4-positive cells, displaying a much more potent effect than the lead compound RB-108. Notably, compound IIIm significantly decreased carrageenan-induced swollen volume and paw thickness in a mouse paw edema model. More importantly, IIIm exhibited satisfying PK profiles with a half-life of 4.77 h in an SD rat model. In summary, we have developed compound IIIm as a new candidate for further investigation based on the lead compound RB-108.

Indexed as

AmidesAnimalsAnti-Inflammatory Agents, Non-SteroidalCarrageenanCell Line, TumorCell ProliferationDisease Models, AnimalDose-Response Relationship, DrugFemaleHumansInflammationMiceMice, Inbred C57BLMolecular StructureRatsRats, Sprague-DawleyAmidesAnti-Inflammatory Agents, Non-SteroidalCarrageenanCXCR4 protein, humanReceptors, CXCR4Anti-inflammationCXCR4 modulatorsInflammatory cell recruitmentRB-108Structural modification

Identifiers

PMID30981691
PMCPMC6488424

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.