Evidence map›Paper›PMID 40754220›Full record

ArticleBioorganic & medicinal chemistry letters2025

Optimization of IRAK1/4/pan-FLT3 kinase inhibitors as treatments for acute myeloid leukemia.

Patrick J Sutter, Morgan M Walker, Chris J Finocchio, Jian-Kang Jiang, Gregory J Tawa, Xiaohu Zhang, Xin Xu, Pranav Shah, Glenn Y Gomba, Daniel T Starczynowski and 2 more

Abstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Patrick J SutterNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States.
Morgan M WalkerNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States.
Chris J FinocchioNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States.
Jian-Kang JiangNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States. Electronic address: jiankang.jiang@nih.gov.
Gregory J TawaNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States.
Xiaohu ZhangNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States.
Xin XuNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States.
Pranav ShahNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States.
Glenn Y GombaNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States.
Daniel T StarczynowskiCincinnati Children's Hospital Medical Center, Division of Experimental Hematology, Cincinnati, OH 45229, United States.
Craig J ThomasNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States; National Cancer Institute, Bethesda, MD 20814, United States.
Scott HoytNational Center for Advancing Translational Sciences, Rockville, MD 20850, United States. Electronic address: scott.hoyt@nih.gov.

Funding

Xenotransplant and Genome Editing CoreU54DK126108 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Daniel Starczynowski, YI ZHENG · 2021 to 2026
$5.0M
Decoding innate immune signaling in normal and myelodysplastic hematopoiesisR35HL135787 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI STARCZYNOWSKI, DANIEL · 2017 to 2022
$4.6M
Therapeutic targeting of IRAK4 in MDSR01CA275007 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI Daniel Starczynowski, Amit K. Verma · 2022 to 2026
$2.6M
The development of multikinase inhibitors for the treatment of selected cancersZIATR000044 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI THOMAS, CRAIG · 2015 to 2022
$1.6M
Intramural NIH HHS Z99 TR999999Intramural NIH HHS ZIA TR000044NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INCI NIH HHS R01 CA275007NHLBI NIH HHS R35 HL135787NIDDK NIH HHS U54 DK126108
6 · The paper itself

Abstract

FLT3 kinase inhibitors have been advanced to the clinic as targeted treatments for acute myeloid leukemia (AML). These inhibitors can produce promising initial responses, but patients often relapse with treatment-resistant disease. A significant factor contributing to relapse involves adaptive signaling through an alternative pathway mediated by IRAK1 and IRAK4 kinases. Compounds that inhibit IRAK1/4 and FLT3 may thus provide superior efficacy relative to compounds that inhibit FLT3 only. We report the optimization of an imidazopyridine series of IRAK1/4/pan-FLT3 kinase inhibitors. Optimization efforts have produced key compound 31, which displays potent inhibition of IRAK1, IRAK4, and FLT3, potent activity in multiple AML tumor cell viability assays, and efficacy superior to that of approved FLT3 inhibitors in multiple mouse xenograft models of AML.

Indexed as

Antineoplastic Agentsfms-Like Tyrosine Kinase 3Interleukin-1 Receptor-Associated KinasesLeukemia, Myeloid, AcuteProtein Kinase InhibitorsAnimalsCell Line, TumorCell ProliferationCell SurvivalDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMiceMolecular StructureStructure-Activity RelationshipAntineoplastic AgentsFLT3 protein, humanfms-Like Tyrosine Kinase 3Interleukin-1 Receptor-Associated KinasesIRAK1 protein, humanIRAK4 protein, humanProtein Kinase InhibitorsAMLFLT3IRAK1IRAK4KinaseLeukemia

Identifiers

PMID40754220
PMCPMC12404068

What Socratic 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 Socratic graph.