Evidence map›Paper›PMID 38116412›Full record

ArticleACS medicinal chemistry letters2023

Kinases Controlling Stability of the Oncogenic MYCN Protein.

Nailah Smith, Eduard Reznik, Brygida Bisikirska, Vasiliki Polychronidou, Qian Wang, Arie Zask, Farhad Forouhar, Andrea Califano, Brent R Stockwell

Open access · greenAbstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 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

9 authors at 2 institutions in 1 country.

Nailah SmithDepartment of Biological Sciences, Columbia University, New York City, New York 10027, United States.
Eduard ReznikDepartment of Biological Sciences, Columbia University, New York City, New York 10027, United States.
Brygida BisikirskaDepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York City, New York 10032, United States.
Vasiliki PolychronidouDepartment of Biological Sciences, Columbia University, New York City, New York 10027, United States.
Qian WangDepartment of Biological Sciences, Columbia University, New York City, New York 10027, United States.
Arie ZaskDepartment of Biological Sciences, Columbia University, New York City, New York 10027, United States.
Farhad ForouharDepartment of Biological Sciences, Columbia University, New York City, New York 10027, United States.
Andrea CalifanoDepartment of Systems Biology, Columbia University Medical Center, New York City, New York 10032, United States.
Brent R StockwellDepartment of Biological Sciences, Columbia University, New York City, New York 10027, United States.ORCID https://orcid.org/0000-0002-3532-3868
Columbia University · USColumbia University Irving Medical Center · US

Funding

Predicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5M
Defining the functions and translational potential of ferroptosisR35CA209896 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI STOCKWELL, BRENT R. · 2016 to 2022
$6.5M
Systematic Identification and Pharmacological Targeting of Tumor Dependencies for Precision Cancer MedicineU01CA217858 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2017 to 2021
$6.1M
Elucidating and Targeting tumor dependencies and drug resistance determinants at the single cell levelU01CA272610 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2022 to 2026
$4.8M
High-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0M
High Performance Computing Cluster for Biomedical ResearchS10OD032433 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2023 to 2023
$2.0M
Storage System for High Performance ComputingS10OD021764 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2016 to 2016
$600k
NCI NIH HHS R35 CA197745NCI NIH HHS R35 CA209896NCI NIH HHS U01 CA217858NCI NIH HHS U01 CA272610NIH HHS S10 OD012351NIH HHS S10 OD021764NIH HHS S10 OD032433
6 · The paper itself

Abstract

We previously identified the natural products isopomiferin and pomiferin as powerful, indirect MYCN-ablating agents. In this work, we expand on their mechanism of action and find that casein kinase 2 (CK2), phosphoinositide 3-kinase (PI3K), checkpoint kinase 1 (CHK1) and serine/threonine protein kinase 38-like (STK38L), as well as STK38, work synchronously to create a field effect that maintains MYCN stability. By systematically inhibiting these kinases, we degraded MYCN and induced cell death. Additionally, we synthesized and tested several simpler and more cost-effective pomiferin analogues, which successfully emulated the compound's MYCN ablating activity. Our work identified and characterized key kinases that can be targeted to interfere with the stability of the MYCN protein in NBL cells, demonstrating the efficacy of an indirect approach to targeting "undruggable" cancer drivers.

Identifiers

PMID38116412
PMCPMC10726605
OpenAlexW4389295960

What OpenQuestion holds

Textmetadata
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.