Evidence map›Paper›PMID 29514916›Full record

ArticleThe Journal of experimental medicine2018

CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss.

Tal Teitz, Jie Fang, Asli N Goktug, Justine D Bonga, Shiyong Diao, Robert A Hazlitt, Luigi Iconaru, Marie Morfouace, Duane Currier, Yinmei Zhou and 11 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% 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

68 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Pooled it
  2. Honokiol-mediated reversal of cisplatin-induced transcriptomic changes in outer hair cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026
    Article
  3. Restoring Iron Homeostasis via Smoothened Inhibition: A Novel Strategy Against Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Therapeutic Potential of MgHNeuroscience bulletin · 2026
    Article
  5. Article
  6. Article
  7. Rational Design of Inner Ear Drug Delivery Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. BRCA1 Promotes Repair of DNA Damage in Cochlear Hair Cells and Prevents Hearing Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

8 more citing papers are in PubMed but not listed here.

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

21 authors at 1 institution in 1 country.

Tal TeitzDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN.
Jie FangDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN.
Asli N GoktugDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN.
Justine D BongaDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN.
Shiyong DiaoDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN.
Robert A HazlittDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN.ORCID 0000-0001-5833-946X
Luigi IconaruDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN.
Marie MorfouaceDepartment of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN.
Duane CurrierDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN.
Yinmei ZhouDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN.
Robyn A UmansDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN.
Michael R TaylorDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN.
Cheng ChengDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN.
Jaeki MinDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN.ORCID 0000-0002-0083-3198
Burgess FreemanPreclinical PK Shared Resource, St. Jude Children's Research Hospital, Memphis, TN.ORCID 0000-0003-2174-5119
Junmin PengDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN.
Martine F RousselDepartment of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN.
Richard KriwackiDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN.
R Kiplin GuyDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN.
Taosheng ChenDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN.
Jian ZuoDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN jian.zuo@stjude.org.ORCID 0000-0002-1448-4507
St. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
The DNA Damage Response and Tumorigenesis in the BrainP01CA096832 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BAKER, SUZANNE J. · 2003 to 2025
$38.0M
Regulation of xenobiotic receptors PXR and CAR: implications in drug dispositionR35GM118041 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Taosheng Chen · 2016 to 2026
$4.3M
GENETIC ANALYSIS OF MAMMALIAN HEARING SENSITIVITYR01DC006471 · NIDCD · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ZUO, JIAN · 2004 to 2013
$3.5M
Genetic control of cellular conversion in the mature cochleaR01DC015010 · NIDCD · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ZUO, JIAN · 2016 to 2020
$2.3M
Discovery of In Vivo Small Molecules for Hearing Protection Against Cisplatin and NoiseR01DC015444 · NIDCD · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ZUO, JIAN · 2016 to 2018
$1.6M
Drug discovery for hair cell regeneration in adult mammalian cochleaeR21DC013879 · NIDCD · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ZUO, JIAN · 2014 to 2015
$479k
NCI NIH HHS P01 CA096832NCI NIH HHS P30 CA021765NIDCD NIH HHS R01 DC006471NIDCD NIH HHS R01 DC015010NIDCD NIH HHS R01 DC015444NIDCD NIH HHS R21 DC013879NIGMS NIH HHS R35 GM118041
6 · The paper itself

Abstract

Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration-approved drugs to prevent or treat it. We screened 4,385 small molecules in a cochlear cell line and identified 10 compounds that protected against cisplatin toxicity in mouse cochlear explants. Among them, kenpaullone, an inhibitor of multiple kinases, including cyclin-dependent kinase 2 (CDK2), protected zebrafish lateral-line neuromasts from cisplatin toxicity and, when delivered locally, protected adult mice and rats against cisplatin- and noise-induced hearing loss. CDK2-deficient mice displayed enhanced resistance to cisplatin toxicity in cochlear explants and to cisplatin- and noise-induced hearing loss in vivo. Mechanistically, we showed that kenpaullone directly inhibits CDK2 kinase activity and reduces cisplatin-induced mitochondrial production of reactive oxygen species, thereby enhancing cell survival. Our experiments have revealed the proapoptotic function of CDK2 in postmitotic cochlear cells and have identified promising therapeutics for preventing hearing loss.

Indexed as

AnimalsBenzazepinesCell DeathCell Line, TumorCisplatinCyclin-Dependent Kinase 2CytoprotectionDrug ResistanceGerm CellsHair Cells, AuditoryHearing Loss, Noise-InducedIndolesLateral Line SystemMice, Inbred C57BLMice, KnockoutMitochondriaBenzazepinesCisplatinCyclin-Dependent Kinase 2IndoleskenpaulloneProtein Kinase InhibitorsReactive Oxygen SpeciesSmall Molecule Libraries

Identifiers

PMID29514916
PMCPMC5881471
OpenAlexW2791394169

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.