ArticleCancer cell international2026
In silico screening, synthesis, and biological evaluation of pyrazolopyrimidine-derived mTOR inhibitors for anticancer and senomorphic effects.
Article in Cancer cell international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
Abstract
backgroundCellular senescence is a stress-induced state characterized by irreversible cell cycle arrest. Senescent cells accumulate during aging and contribute to age-related diseases, including neurodegeneration, cancer, and type 2 diabetes mellitus. The mTOR signaling pathway plays a critical role in maintaining and regulating senescence-associated features.
methodsWe employed virtual high-throughput screening and fragment-based design to identify novel small-molecule competitive mTOR kinase inhibitors with favorable physicochemical properties. Six lead compounds (1-6) were selected, and torkinib (7) was synthesized and used as a reference.
resultsBiochemical and cell-based assays revealed that torkinib and compounds 5 and 6 inhibited mTORC1-mediated phosphorylation of p70 S6K. Compound 5 exhibited cytostatic effects in both non-transformed human cells and glioma cancer cells, with greater sensitivity observed in the latter. Unlike the rapalog temsirolimus, both torkinib and compound 5 suppressed migration in multiple glioblastoma cell lines. Notably, compound 5 induced a transient autophagy flux distinct from that elicited by other tested mTOR inhibitors. Furthermore, compound 5 reduced radiation-induced expression of senescence-associated secretory phenotype (SASP) markers, including IL-1α, IL-6, and IL-8. Additional senomorphic effects included decreased cell size and reduced senescence-associated β-galactosidase activity. In vivo, compound 5 showed slightly higher toxicity than torkinib, likely due to improved solubility.
conclusionsCompound 5 demonstrates distinct biological effects compared to torkinib and represents a promising candidate for further development as an mTOR inhibitor targeting both cancer and senescent cells.
Indexed as
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.