ArticleCell death discovery2022
GNE-493 inhibits prostate cancer cell growth via Akt-mTOR-dependent and -independent mechanisms.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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.
Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- The role of reactive oxygen species in the transformation from prostatitis to prostate cancer: a review.Frontiers in immunology · 2025Review
- KCNAB2 overexpression inhibits human non-small-cell lung cancer cell growth in vitro and in vivo.Cell death discovery · 2023Article
- Identification of the mitochondrial protein POLRMT as a potential therapeutic target of prostate cancer.Cell death & disease · 2023Article
- Targeting PI3K/Akt signaling in prostate cancer therapy.Journal of cell communication and signaling · 2023Review
- Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth.Cell death & disease · 2023Article
- A first-in-class HBO1 inhibitor WM-3835 inhibits castration-resistant prostate cancer cell growth in vitro and in vivo.Cell death & disease · 2023Article
- Advances in the regulatory mechanisms of mTOR in necroptosis.Frontiers in immunology · 2023Review
- From Therapy Resistance to Targeted Therapies in Prostate Cancer.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
GNE-493 is a novel PI3K/mTOR dual inhibitor with improved metabolic stability, oral bioavailability, and excellent pharmacokinetic parameters. Here GNE-493 potently inhibited viability, proliferation, and migration in different primary and established (LNCaP and PC-3 lines) prostate cancer cells, and provoking apoptosis. GNE-493 blocked Akt-mTOR activation in primary human prostate cancer cells. A constitutively-active mutant Akt1 restored Akt-mTOR activation but only partially ameliorated GNE-493-induced prostate cancer cell death. Moreover, GNE-493 was still cytotoxic in Akt1/2-silenced primary prostate cancer cells. Significant oxidative stress and programmed necrosis cascade activation were detected in GNE-493-treated prostate cancer cells. Moreover, GNE-493 downregulated Sphingosine Kinase 1 (SphK1), causing ceramide accumulation in primary prostate cancer cells. Daily single dose GNE-493 oral administration robustly inhibited the growth of the prostate cancer xenograft in the nude mice. Akt-mTOR inactivation, SphK1 downregulation, ceramide level increase, and oxidative injury were detected in GNE-493-treated prostate cancer xenograft tissues. Together, GNE-493 inhibited prostate cancer cell growth possibly through the Akt-mTOR-dependent and -independent mechanisms.
Identifiers
What OpenQuestion holds
Registered trials
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.