Evidence map›Paper›PMID 38950330›Full record

ArticleThe Journal of clinical investigation2024

Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia.

Baskar Ramdas, Neetu Dayal, Ruchi Pandey, Elizabeth Larocque, Rahul Kanumuri, Santhosh Kumar Pasupuleti, Sheng Liu, Chrysi Kanellopoulou, Elizabeth Fei Yin Chu, Rodrigo Mohallem and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

21 authors.

Baskar RamdasDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Neetu DayalDepartment of Chemistry, Purdue University, West Lafayette, Indiana, USA.
Ruchi PandeyDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Elizabeth LarocqueDepartment of Chemistry, Purdue University, West Lafayette, Indiana, USA.
Rahul KanumuriDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Santhosh Kumar PasupuletiDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Chrysi KanellopoulouKinaRx, Inc, Rockville, Maryland, USA.
Elizabeth Fei Yin ChuDepartment of Chemistry, Purdue University, West Lafayette, Indiana, USA.
Rodrigo MohallemDepartment of Comparative Pathobiology.
Saniya ViraniDepartment of Chemistry, Purdue University, West Lafayette, Indiana, USA.
Gaurav ChopraDepartment of Chemistry, Purdue University, West Lafayette, Indiana, USA.
Uma K AryalDepartment of Comparative Pathobiology.
Rena LapidusKinaRx, Inc, Rockville, Maryland, USA.
Jun WanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Ashkan EmadiKinaRx, Inc, Rockville, Maryland, USA.
Laura S HanelineDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Frederick W HoltsbergKinaRx, Inc, Rockville, Maryland, USA.
M Javad AmanKinaRx, Inc, Rockville, Maryland, USA.
Herman O SintimDepartment of Chemistry, Purdue University, West Lafayette, Indiana, USA.
Reuben KapurDepartment of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Sara K Quinney · 1999 to 2026
$59.3M
Project-005U54DK106846 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Reuben Kapur, Karen Elizabeth Pollok · 2015 to 2026
$9.7M
Role of p21 activated kinase in LeukemogenesisR01CA173852 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI KAPUR, REUBEN · 2014 to 2025
$3.4M
Role of Shp2 in FLT3-ITD-Induced LeukemogenesisR01CA134777 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI KAPUR, REUBEN · 2011 to 2023
$3.4M
Hyperglycemia mediated myeloproliferative diseaseR01HL140961 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI KAPUR, REUBEN · 2019 to 2022
$2.3M
Third line treatment of drug resistant FLT3-positive acute myeloid leukemia with a novel FLT3 kinase inhibitorR44CA247134 · NCI · KINARX, LLC · PI HOLTSBERG, FREDERICK WAYNE, SINTIM, HERMAN O · 2020 to 2021
$2.0M
In Vivo Fluorescence and Bioluminescence Imager with CTS10OD030430 · OD · UNIVERSITY OF MARYLAND BALTIMORE · PI LAPIDUS, RENA · 2021 to 2021
$600k
NCI NIH HHS P30 CA082709NCI NIH HHS R01 CA134777NCI NIH HHS R01 CA173852NCI NIH HHS R44 CA247134NHLBI NIH HHS R01 HL140961NIDDK NIH HHS U54 DK106846NIH HHS S10 OD030430
6 · The paper itself

Abstract

Activating mutations of FLT3 contribute to deregulated hematopoietic stem and progenitor cell (HSC/Ps) growth and survival in patients with acute myeloid leukemia (AML), leading to poor overall survival. AML patients treated with investigational drugs targeting mutant FLT3, including Quizartinib and Crenolanib, develop resistance to these drugs. Development of resistance is largely due to acquisition of cooccurring mutations and activation of additional survival pathways, as well as emergence of additional FLT3 mutations. Despite the high prevalence of FLT3 mutations and their clinical significance in AML, there are few targeted therapeutic options available. We have identified 2 novel nicotinamide-based FLT3 inhibitors (HSN608 and HSN748) that target FLT3 mutations at subnanomolar concentrations and are potently effective against drug-resistant secondary mutations of FLT3. These compounds show antileukemic activity against FLT3ITD in drug-resistant AML, relapsed/refractory AML, and in AML bearing a combination of epigenetic mutations of TET2 along with FLT3ITD. We demonstrate that HSN748 outperformed the FDA-approved FLT3 inhibitor Gilteritinib in terms of inhibitory activity against FLT3ITD in vivo.

Indexed as

Drug Resistance, Neoplasmfms-Like Tyrosine Kinase 3Leukemia, Myeloid, AcuteNiacinamideAnimalsAntineoplastic AgentsCell Line, TumorFemaleHumansMiceMice, Inbred NODMice, SCIDMutationXenograft Model Antitumor AssaysAntineoplastic AgentsFLT3 protein, humanfms-Like Tyrosine Kinase 3NiacinamideHematologyHematopoietic stem cellsStem cells

Identifiers

PMID38950330
PMCPMC11178545

What OpenQuestion holds

Textmetadata
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.