Evidence map›Paper›PMID 36599397›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2023

Targeting BRD4 and PI3K signaling pathways for the treatment of medulloblastoma.

Bharti Sethi, Virender Kumar, Thilina D Jayasinghe, Yuxiang Dong, Donald R Ronning, Haizhen A Zhong, Donald W Coulter, Ram I Mahato

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Lipid nanomedicine simultaneously inhibits BRD4/PI3K and MDM2/XIAP signaling pathways for effective treatment of Medulloblastoma.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  3. COG133 peptide-conjugated lipid nanoparticles sensitize medulloblastoma to radiation therapy in mice.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  4. Article
  5. Drug and nucleic acid delivery and targeting to the brain.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Article
  6. 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

8 authors at 2 institutions in 1 country.

Bharti SethiDepartment of Pharmaceutical Sciences, the University of Nebraska Medical Center, Omaha, NE 68198, USA.
Virender KumarDepartment of Pharmaceutical Sciences, the University of Nebraska Medical Center, Omaha, NE 68198, USA.
Thilina D JayasingheDepartment of Pharmaceutical Sciences, the University of Nebraska Medical Center, Omaha, NE 68198, USA.
Yuxiang DongDepartment of Pharmaceutical Sciences, the University of Nebraska Medical Center, Omaha, NE 68198, USA.
Donald R RonningDepartment of Pharmaceutical Sciences, the University of Nebraska Medical Center, Omaha, NE 68198, USA.
Haizhen A ZhongDepartment of Chemistry, the University of Nebraska at Omaha, 6001 Dodge Street, Omaha, NE 68182, USA.
Donald W CoulterDepartment of Pediatrics, the University of Nebraska Medical Center, Omaha, NE 68198, USA.
Ram I MahatoDepartment of Pharmaceutical Sciences, the University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: ram.mahato@unmc.edu.
University of Nebraska Medical Center · USUniversity of Nebraska at Omaha · US

Funding

Lipid nanomedicine targeting multiple signaling pathways of medulloblastomaR01NS128336 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Ram I. Mahato · 2022 to 2026
$2.4M
Nanomedicine of Hedgehog and AKT/ERK Dual Inhibitors for Pancreatic CancerR01CA266759 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Ram I. Mahato · 2022 to 2026
$2.2M
Overcoming Resistance Mechanisms in Hedgehog and Myc-amplified MedulloblastomaR01NS116037 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI COULTER, DONALD, MAHATO, RAM I. · 2021 to 2025
$1.9M
Development and Preclinical Evaluation of Nanoformulations in Liver Fibrotic MiceR01DK135817 · NIDDK · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Ram I. Mahato, NATALIA ALEKSANDR OSNA · 2023 to 2026
$1.6M
NCI NIH HHS R01 CA266759NIDDK NIH HHS R01 DK135817NINDS NIH HHS R01 NS116037NINDS NIH HHS R01 NS128336
6 · The paper itself

Abstract

Medulloblastoma (MB) is a malignant pediatric brain tumor which shows upregulation of MYC and sonic hedgehog (SHH) signaling. SHH inhibitors face acquired resistance, which is a major cause of relapse. Further, direct MYC oncogene inhibition is challenging, inhibition of MYC upstream insulin-like growth factor/ phosphatidylinositol-4,5-bisphosphate 3-kinase (IGF/PI3K) is a promising alternative. While PI3K inhibition activates resistance mechanisms, simultaneous inhibition of bromodomain-containing protein 4 (BRD4) and PI3K can overcome resistance. We synthesized a new molecule 8-(2,3-dihydrobenzo[b] [1, 4] dioxin-6-yl)-2-morpholino-4H-chromen-4-one (MDP5) that targets both BRD4 and PI3K pathways. We used X-ray crystal structures and a molecular modeling approach to confirm the interactions between MDP5 with bromo domains (BDs) from both BRD2 and BRD4, and molecular modeling for PI3K binding. MDP5 was shown to inhibit target pathways and MB cell growth in vitro and in vivo. MDP5 showed higher potency in DAOY cells (IC

Indexed as

Brain NeoplasmsCerebellar NeoplasmsMedulloblastomaAnimalsBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorCell ProliferationHedgehog ProteinsHumansMiceNuclear ProteinsPhosphatidylinositol 3-KinasesSignal TransductionTranscription FactorsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsHedgehog ProteinsNuclear ProteinsPhosphatidylinositol 3-KinasesTranscription FactorsBRD4 inhibitorChemoresistanceCrystal structureMDP5Medulloblastoma

Identifiers

PMID36599397
PMCPMC9974792
OpenAlexW4313545217

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.