Evidence map›Paper›PMID 40007440›Full record

ArticleMolecular oncology2025

Thermal proteome profiling and proteome analysis using high-definition mass spectrometry demonstrate modulation of cholesterol biosynthesis by next-generation galeterone analog VNPP433-3β in castration-resistant prostate cancer.

Retheesh S Thankan, Elizabeth Thomas, Mehari M Weldemariam, Puranik Purushottamachar, Weiliang Huang, Maureen A Kane, Yuji Zhang, Nicholas Ambulos, Bi-Dar Wang, David Weber and 1 more

Abstract read
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In one paragraph

Article in Molecular oncology, 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. 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

11 authors.

Retheesh S ThankanDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.
Elizabeth ThomasDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID https://orcid.org/0000-0002-3759-4047
Mehari M WeldemariamDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Puranik PurushottamacharDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.
Weiliang HuangDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Maureen A KaneDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Yuji ZhangDivision of Biostatistics and Bioinformatics, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Nicholas AmbulosDepartment of Microbiology and Immunology, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Bi-Dar WangDepartment of Pharmaceutical Sciences, School of Pharmacy and Health Professions, University of Maryland Eastern Shore, Princess Anne, MD, USA.
David WeberThe Center for Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD, USA.
Vincent C O NjarDepartment of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID https://orcid.org/0000-0003-2630-8479

Funding

Development of Next Generation Galeterone Analogs for Prostate Cancer TherapyR01CA224696 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI NJAR, VINCENT COLLINS OFUKA · 2018 to 2022
$2.6M
Aberrant Splice Variants as Potential Precision Biomarkers for Aggressive Prostate Cancers in African American PatientsSC1GM127256 · NIGMS · UNIVERSITY OF MARYLAND EASTERN SHORE · PI WANG, BI-DAR · 2019 to 2022
$1.6M
National Institutes of Health (NIH), USA and the National Cancer Institute (NCI), USA R01CA224696NCI NIH HHS R01 CA224696NIGMS NIH HHS SC1 GM127256
6 · The paper itself

Abstract

Cholesterol (CHOL) homeostasis is significantly modulated in prostate cancer (PCa) suggesting an active role in PCa development and progression. Several studies indicate a strong correlation between elevated CHOL levels and increased PCa risk and severity. Inhibition of CHOL biosynthesis at different steps, including lanosterol synthase (LSS), has shown significant efficacy against both hormone-dependent and castration-resistant PCa. Earlier, we reported proteasomal degradation of androgen receptor (AR)/AR-Vs and Mnk1/2 as the primary mechanisms of action of VNPP433-3β in inhibiting PCa cell proliferation and tumor growth. Through thermal proteome profiling, comparative proteomics and cellular thermal shift assay, we identified VNPP433-3β's ancillary effect of lowering CHOL by binding to LSS and lanosterol 14-alpha demethylase, potentially inhibiting CHOL biosynthesis in PCa cells and tumors. Additionally, in conjunction with our previously reported transcriptome analysis, proteomics reveals that VNPP433-3β modulated upstream regulators and pathways critical for PCa stem cell maintenance and recurrence. The inhibition of CHOL biosynthesis by VNPP433-3β reinforces its multifaceted effects in PCa across all stages, highlighting its potential as a single-agent therapy. Achieving reduced CHOL levels aligns with better treatment outcomes, further substantiating VNPP433-3β's therapeutic potential.

Indexed as

CholesterolMass SpectrometryProstatic Neoplasms, Castration-ResistantProteomeProteomicsAndrostadienesAnimalsCell Line, TumorCell ProliferationHumansImidazolesMaleMiceAndrostadienesCholesterolImidazolesProteomeVNPP433-3betacholesterolCYP51A1lanosterol synthasenext‐generation galeterone analogprostate cancerthermal proteome profiling

Identifiers

PMID40007440
PMCPMC12330945

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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.