Evidence map›Paper›PMID 33392507›Full record

ArticleNeuro-oncology advances

Pharmacokinetic properties of the temozolomide perillyl alcohol conjugate (NEO212) in mice.

Hee-Yeon Cho, Steve Swenson, Thu Zan Thein, Weijun Wang, Neloni R Wijeratne, Nagore I Marín-Ramos, Jonathan E Katz, Florence M Hofman, Axel H Schönthal, Thomas C Chen

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

Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Enhancing temozolomideAsian journal of pharmaceutical sciences · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
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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

10 authors at 1 institution in 1 country.

Hee-Yeon ChoDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Steve SwensonDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Thu Zan TheinDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Weijun WangDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.ORCID 0000-0002-7430-5937
Neloni R WijeratneLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, California, USA.
Nagore I Marín-RamosDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Jonathan E KatzLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, California, USA.
Florence M HofmanDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Axel H SchönthalDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Thomas C ChenDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
University of Southern California · US

Funding

Temozolomide Perillyl Alcohol Conjugate as Treatment for Recurrent Malignant Brain tumorsR41CA192419 · NCI · NEONC TECHNOLOGIES, INC. · PI CHEN, THOMAS C., HOFMAN, FLORENCE M · 2016 to 2016
$300k
NCI NIH HHS R41 CA192419
6 · The paper itself

Abstract

backgroundNEO212 is a novel small-molecule anticancer agent that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH) to the alkylating agent temozolomide (TMZ). It is undergoing preclinical development as a therapeutic for brain-localized malignancies. The aim of this study was to characterize metabolism and pharmacokinetic (PK) properties of NEO212 in preclinical models.

methodsWe used mass spectrometry (MS) and modified high-performance liquid chromatography to identify and quantitate NEO212 and its metabolites in cultured glioblastoma cells, in mouse plasma, brain, and excreta after oral gavage.

resultsOur methods allowed identification and quantitation of NEO212, POH, TMZ, as well as primary metabolites 5-aminoimidazole-4-carboxamide (AIC) and perillic acid (PA). Intracellular concentrations of TMZ were greater after treatment of U251TR cells with NEO212 than after treatment with TMZ. The half-life of NEO212 in mouse plasma was 94 min. In mice harboring syngeneic GL261 brain tumors, the amount of NEO212 was greater in the tumor-bearing hemisphere than in the contralateral normal hemisphere. The brain:plasma ratio of NEO212 was greater than that of TMZ. Excretion of unaltered NEO212 was through feces, whereas its AIC metabolite was excreted via urine.

conclusionsNEO212 preferentially concentrates in brain tumor tissue over normal brain tissue, and compared to TMZ has a higher brain:plasma ratio, altogether revealing favorable features to encourage its further development as a brain-targeted therapeutic. Its breakdown into well-characterized, long-lived metabolites, in particular AIC and PA, will provide useful equivalents for PK studies during further drug development and clinical trials with NEO212.

Indexed as

glioblastomaHPLCNEO212pharmacokinetictemozolomide

Identifiers

PMID33392507
PMCPMC7764505
OpenAlexW3114387541

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

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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.