Evidence map›Paper›PMID 34971957›Full record

ArticleBiochemical and biophysical research communications2022

CN470 is a BET/CBP/p300 multi-bromodomain inhibitor and has an anti-tumor activity against MLL-rearranged acute lymphoblastic leukemia.

Natsuki Imayoshi, Makoto Yoshioka, Kuniaki Tanaka, Shyh-Ming Yang, Koshi Akahane, Yuki Toda, Shigekuni Hosogi, Takeshi Inukai, Seiji Okada, David J Maloney and 4 more

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

Article in Biochemical and biophysical research communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Depletion ofCancer genomics & proteomics
    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 5 institutions in 2 countries.

Natsuki ImayoshiDepartment of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan; DC1, Japan Society for the Promotion of Science, Tokyo, Japan.
Makoto YoshiokaConverGene LLC, Cambridge, MD, USA.
Kuniaki TanakaDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Shyh-Ming YangNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Koshi AkahaneDepartment of Pediatrics, School of Medicine, University of Yamanashi, Yamanashi, Japan.
Yuki TodaDepartment of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Shigekuni HosogiDepartment of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Takeshi InukaiDepartment of Pediatrics, School of Medicine, University of Yamanashi, Yamanashi, Japan.
Seiji OkadaDivision of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto, Japan.
David J MaloneyNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Tatsutoshi NakahataDrug Discovery Technology Development Office, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Junko TakitaDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Itaru KatoDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Eishi AshiharaDepartment of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan. Electronic address: ash@mb.kyoto-phu.ac.jp.
Kyoto University · JPKyoto Pharmaceutical University · JPNational Institutes of Health · USUniversity of Yamanashi · JPJapan Society for the Promotion of Science · JP

Funding

Intramural NIH HHS Z99 TR999999
6 · The paper itself

Abstract

Acute lymphoblastic leukemia with chromosomal rearrangements involving the mixed-lineage leukemia (MLL) gene (MLL-r ALL) remains an incurable disease. Thus, development of a safe and effective therapeutic agent to treat this disease is crucial to address this unmet medical need. BRD4, a member of the bromodomain and extra-terminal domain (BET) protein family, and cyclic AMP response element binding protein binding protein (CBP) and p300, two paralogous histone acetyltransferases, are all considered cancer drug targets and simultaneous targeting of these proteins may have therapeutic advantages. Here, we demonstrate that a BET/CBP/p300 multi-bromodomain inhibitor, CN470, has anti-tumor activity against MLL-r ALL in vitro and in vivo. CN470, potently inhibited ligand binding to the bromodomains of BRD4, CBP, and p300 and suppressed the growth of MLL-r ALL cell lines and patient-derived cells with MLL rearrangements. CN470 suppressed mRNA and protein expression of MYC and induced apoptosis in MLL-r ALL cells, following a cell cycle arrest in the G1 phase. Moreover, CN470 reduced BRD4 binding to acetylated histone H3. The in vivo effects of CN470 were investigated using SEM

Indexed as

Gene RearrangementAnimalsAntineoplastic AgentsApoptosisCell Cycle CheckpointsCell Line, TumorCell ProliferationE1A-Associated p300 ProteinGene Expression Regulation, LeukemicHistone-Lysine N-MethyltransferaseHumansMiceMyeloid-Lymphoid Leukemia ProteinPrecursor Cell Lymphoblastic Leukemia-LymphomaRNA, MessengerSurvival AnalysisAntineoplastic AgentsE1A-Associated p300 ProteinEP300 protein, humanHistone-Lysine N-MethyltransferaseKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinRNA, MessengerALLBETBromodomainCBP/p300MLLPDX

Identifiers

PMID34971957
PMCPMC8898544
OpenAlexW4200154849

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.