Evidence map›Paper›PMID 35031886›Full record

ArticleMolecular biomedicine2022

Combinatorial inhibition of BTK, PI3K-AKT and BRD4-MYC as a strategy for treatment of mantle cell lymphoma.

Kendra R Vann, Dhananjaya Pal, Audrey L Smith, Namood-E Sahar, Maddeboina Krishnaiah, Dalia El-Gamal, Tatiana G Kutateladze

Open access · diamondAbstract read
In one paragraph

Article in Molecular biomedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 28% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

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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

7 authors at 5 institutions in 1 country.

Kendra R Vann *Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA.
Dhananjaya Pal *Molecular Targeted Therapeutics Laboratory, Levine Cancer Institute, Charlotte, NC, USA.
Audrey L SmithEppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Namood-E SaharDivision of Hematology and Oncology, Department of Pediatrics, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Maddeboina KrishnaiahMolecular Targeted Therapeutics Laboratory, Levine Cancer Institute, Charlotte, NC, USA.
Dalia El-GamalEppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Tatiana G KutateladzeDepartment of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA. tatiana.kutateladze@cuanschutz.edu.ORCID http://orcid.org/0000-0001-7375-6990
Target (United States) · USUniversity of Nebraska Medical Center · USUniversity of California San Diego · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · US

Funding

Targeting acetylated histone H4 by MLL4R01AG067664 · NIA · UNIVERSITY OF COLORADO DENVER · PI KUTATELADZE, TATIANA G · 2021 to 2025
$2.1M
Molecular analysis of ASH1LR01CA252707 · NCI · UNIVERSITY OF COLORADO DENVER · PI TATIANA G KUTATELADZE · 2020 to 2026
$1.9M
The role of JADE in HBO complexesR01HL151334 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI KUTATELADZE, TATIANA G · 2020 to 2023
$1.8M
Epigenetic mechanisms for regulation of p300R01GM135671 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI KUTATELADZE, TATIANA G · 2020 to 2023
$1.4M
Interdomain crosstalk in MORC3R01GM125195 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI KUTATELADZE, TATIANA G · 2017 to 2021
$1.3M
NCI NIH HHS R01 CA252707NHLBI NIH HHS R01 HL151334NIGMS NIH HHS R01 GM125195NIGMS NIH HHS R01 GM135671
6 · The paper itself

Abstract

Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin's lymphoma characterized by poor prognosis. The complexity of MCL pathogenesis arises from aberrant activities of diverse signaling pathways, including BTK, PI3K-AKT-mTOR and MYC-BRD4. Here, we report that MCL-related signaling pathways can be altered by a single small molecule inhibitor, SRX3305. Binding and kinase activities along with resonance changes in NMR experiments reveal that SRX3305 targets both bromodomains of BRD4 and is highly potent in inhibition of the PI3K isoforms α, γ and δ, as well as BTK and the drug-resistant BTK mutant. Preclinical investigations herein reveal that SRX3305 perturbs the cell cycle, promotes apoptosis in MCL cell lines and shows dose dependent anti-proliferative activity in both MCL and drug-resistant MCL cells. Our findings underscore the effectiveness of novel multi-action small molecule inhibitors for potential treatment of MCL.

Indexed as

BRD4BromodomainBruton's tyrosine kinaseInhibitorMantle cell lymphomaPhosphatidylinositol-3 kinase

Identifiers

PMID35031886
PMCPMC8760370
OpenAlexW4205238556

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.