Evidence map›Paper›PMID 35930851›Full record

ArticleBioorganic & medicinal chemistry2022

Structure-Activity relationship of 1-(Furan-2ylmethyl)Pyrrolidine-Based Stimulation-2 (ST2) inhibitors for treating graft versus host disease.

Xinrui Yuan, Hua Jiang, Denggang Fu, Aaron Robida, Krishani Rajanayake, Hebao Yuan, Bo Wen, Duxin Sun, Brennan T Watch, Krishnapriya Chinnaswamy and 4 more

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

Article in Bioorganic & medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. 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

14 authors at 3 institutions in 1 country.

Xinrui YuanDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United States.
Hua JiangDepartment of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC, United States.
Denggang FuDepartment of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC, United States.
Aaron RobidaLife Sciences Institute, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Krishani RajanayakeRogel Cancer Center, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Pharmaceutical Sciences, College of Pharmacy, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Hebao YuanRogel Cancer Center, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Pharmaceutical Sciences, College of Pharmacy, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Bo WenRogel Cancer Center, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Pharmaceutical Sciences, College of Pharmacy, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Duxin SunRogel Cancer Center, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Pharmaceutical Sciences, College of Pharmacy, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Brennan T WatchMichigan Center for Therapeutic Innovation, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Krishnapriya ChinnaswamyLife Sciences Institute, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Rogel Cancer Center, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Jeanne A StuckeyLife Sciences Institute, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Rogel Cancer Center, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States.
Sophie PaczesnyDepartment of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC, United States.
Jason C RechMichigan Center for Therapeutic Innovation, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI, United States. Electronic address: jcrech@med.umich.edu.
Chao-Yie YangDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United States. Electronic address: cyang26@uthsc.edu.
University of Michigan–Ann Arbor · USMedical University of South Carolina · USUniversity of Tennessee Health Science Center · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
Development of first-in-class ST2 inhibitors for treating graft-versus-host diseaseR01HL141432 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI PACZESNY, SOPHIE, YANG, CHAO-YIE · 2019 to 2022
$2.6M
NCI NIH HHS P30 CA046592NHLBI NIH HHS R01 HL141432
6 · The paper itself

Abstract

An elevated plasma level of soluble ST2 (sST2) is a risk biomarker for graft-versus-host disease (GVHD) and death in patients receiving hematopoietic cell transplantation (HCT). sST2 functions as a trap for IL-33 and amplifies the pro-inflammatory type 1 and 17 response while suppressing the tolerogenic type 2 and regulatory T cells activation during GVHD development. We previously identified small-molecule ST2 inhibitors particularly iST2-1 that reduces plasma sST2 levels and improved survival in two animal models. Here, we reported the structure-activity relationship of the furanylmethylpyrrolidine-based ST2 inhibitors based on iST2-1. Based on the biochemical AlphaLISA assay, we improved the activity of iST2-1 by 6-fold (∼6 μM in IC

Indexed as

Graft vs Host DiseaseAnimalsCD8-Positive T-LymphocytesFuransInterleukin-1 Receptor-Like 1 ProteinInterleukin-33PyrrolidinesStructure-Activity RelationshipFuransInterleukin-1 Receptor-Like 1 ProteinInterleukin-33PyrrolidinesAlphaLISACytokineCytokine receptorGraft versus host diseaseHematopoietic cell transplantationIL33iST2-1Mixed lymphocyte reactionPharmacokineticsSmall-molecule inhibitorsoluble ST2ST2

Identifiers

PMID35930851
PMCPMC9451522
OpenAlexW4286567608

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.