Evidence map›Paper›PMID 40157536›Full record

ArticleThe Journal of biological chemistry2025

Discovery of potent and selective PROTACs for the protein kinase LZK for the treatment of head and neck cancer.

Meghri Katerji, Knickole L Bergman, Eric Lindberg, Maxine R Rubin, Marwa Afifi, Amy L Funk, Carolyn C Woodroofe, Katherine Nyswaner, Kamila Karpińska, Remigiusz Serwa and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Review
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.

Meghri KaterjiLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA.
Knickole L BergmanLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA.
Eric LindbergChemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland, USA.
Maxine R RubinLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA.
Marwa AfifiLaboratory of Cancer Genetics and Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Amy L FunkLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA.
Carolyn C WoodroofeChemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland, USA.
Katherine NyswanerLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA.
Kamila KarpińskaLaboratory of Molecular OncoSignalling, IMol Polish Academy of Sciences, Warsaw, Poland.
Remigiusz SerwaProteomic Core Facility, IMol Polish Academy of Sciences, Warsaw, Poland.
Steven D CappellLaboratory of Cancer Genetics and Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Anna MarusiakLaboratory of Molecular OncoSignalling, IMol Polish Academy of Sciences, Warsaw, Poland.
Rolf E SwensonChemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland, USA. Electronic address: rolf.swenson@nih.gov.
John F BrognardLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA. Electronic address: john.brognard@nih.gov.

Funding

Oncogenic Kinases in CancerZIABC011691 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BROGNARD, JOHN · 2016 to 2025
$14.4M
Intramural NIH HHS ZIA BC011691
6 · The paper itself

Abstract

Leucine zipper-bearing kinase (LZK) is overexpressed in 20% of head and neck squamous cell carcinoma (HNSCC) cases and has emerged as a promising therapeutic target in this cancer subtype. LZK promotes HNSCC survival and proliferation by stabilizing c-MYC and GOF-p53 in kinase-dependent and -independent manners, respectively. Herein, we developed a new series of LZK degraders utilizing proteolysis-targeting chimera (PROTAC) technology by modulating the linker region or LZK warhead of LZK-targeting PROTAC-21A, previously developed by our laboratory. Among the 27 PROTACs synthesized and tested, PROTAC 17 was found to be the most potent, degrading LZK at 250 nM and suppressing HNSCC viability at 500 nM. In summary, our lead PROTAC effectively targeted LZK for proteasomal degradation and inhibited oncogenic activity in HNSCC cell lines with amplified LZK.

Indexed as

Antineoplastic AgentsHead and Neck NeoplasmsProtein Kinase InhibitorsProteolysisCell Line, TumorCell ProliferationHumansProteasome Endopeptidase ComplexProteolysis Targeting ChimeraSquamous Cell Carcinoma of Head and NeckAntineoplastic AgentsProteasome Endopeptidase ComplexProtein Kinase InhibitorsProteolysis Targeting Chimeracancer therapyHNSCCLZKnoncatalytic functionsPROTACproteasomeprotein degradationprotein kinase

Identifiers

PMID40157536
PMCPMC12135360

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.