Evidence map›Paper›PMID 30837643›Full record

ArticleScientific reports2019

Effect of CHK1 Inhibition on CPX-351 Cytotoxicity in vitro and ex vivo.

Nicole D Vincelette, Husheng Ding, Amelia M Huehls, Karen S Flatten, Rebecca L Kelly, Mira A Kohorst, Jonathan Webster, Allan D Hess, Keith W Pratz, Larry M Karnitz and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 21% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Ceramide nanoliposomes augment the efficacy of venetoclax and cytarabine in models of acute myeloid leukemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  8. Review
  9. Article
  10. 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

11 authors at 3 institutions in 1 country.

Nicole D VinceletteDepartment of Molecular Pharmacology, Mayo Clinic, Rochester, MN, USA.
Husheng DingDivision of Oncology Research, Mayo Clinic, Rochester, MN, USA.
Amelia M HuehlsDivision of Oncology Research, Mayo Clinic, Rochester, MN, USA.
Karen S FlattenDivision of Oncology Research, Mayo Clinic, Rochester, MN, USA.
Rebecca L KellyDepartment of Molecular Pharmacology, Mayo Clinic, Rochester, MN, USA.
Mira A KohorstDepartment of Pediatrics, Mayo Clinic, Rochester, MN, USA.
Jonathan WebsterSidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Allan D HessSidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Keith W PratzSidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Larry M KarnitzDepartment of Molecular Pharmacology, Mayo Clinic, Rochester, MN, USA. Karnitz.Larry@Mayo.edu.
Scott H KaufmannDepartment of Molecular Pharmacology, Mayo Clinic, Rochester, MN, USA. Kaufmann.Scott@Mayo.edu.ORCID 0000-0002-4900-7145
Mayo Clinic · USMayo Clinic in Arizona · USSidney Kimmel Cancer Center · US

Funding

Predoctoral Training Program in Molecular PharmacologyT32GM072474 · NIGMS · MAYO CLINIC ROCHESTER · PI KARNITZ, LARRY M · 2005 to 2020
$2.4M
Targeting Chk1 in Acute Myeloid LeukemiaR01CA190473 · NCI · MAYO CLINIC ROCHESTER · PI KARNITZ, LARRY M · 2015 to 2019
$1.8M
Pharmacogenomic regulation of CYP transcription by TSPYL genesR01GM125633 · NIGMS · MAYO CLINIC ROCHESTER · PI WANG, LIEWEI · 2018 to 2021
$1.2M
NCI NIH HHS R01 CA190473NIGMS NIH HHS R01 GM125633NIGMS NIH HHS T32 GM072474U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) T32 GM125633
6 · The paper itself

Abstract

CPX-351 is a liposomally encapsulated 5:1 molar ratio of cytarabine and daunorubicin that recently received regulatory approval for the treatment of therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes based on improved overall survival compared to standard cytarabine/daunorubicin therapy. Checkpoint kinase 1 (CHK1), which is activated by DNA damage and replication stress, diminishes sensitivity to cytarabine and anthracyclines as single agents, suggesting that CHK1 inhibitors might increase the effectiveness of CPX-351. The present studies show that CPX-351 activates CHK1 as well as the S and G2/M cell cycle checkpoints. Conversely, CHK1 inhibition diminishes the cell cycle effects of CPX-351. Moreover, CHK1 knockdown or addition of a CHK1 inhibitor such as MK-8776, rabusertib or prexasertib enhances CPX-351-induced apoptosis in multiple TP53-null and TP53-wildtype AML cell lines. Likewise, CHK1 inhibition increases the antiproliferative effect of CPX-351 on primary AML specimens ex vivo, offering the possibility that CPX-351 may be well suited to combine with CHK1-targeted agents.

Indexed as

ApoptosisCell ProliferationCheckpoint Kinase 1CytarabineDaunorubicinG2 Phase Cell Cycle CheckpointsHumansIn Vitro TechniquesLeukemia, Myeloid, AcuteLeukocytes, MononuclearProtein Kinase InhibitorsTumor Cells, CulturedCheckpoint Kinase 1CHEK1 protein, humanCPX-351CytarabineDaunorubicinProtein Kinase Inhibitors

Identifiers

PMID30837643
PMCPMC6400938
OpenAlexW2919741133

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.