ArticleFrontiers in chemistry2025
Computational advances in the design and discovery of artemis inhibitors for radiosensitization in cancer therapy.
Article in Frontiers in chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Artemis is a key scaffold repair protein involved in the non-homologous end-joining (NHEJ) DNA repair pathway and is encoded by the DCLRE1C gene in humans. Its inhibition disrupts double-strand break (DSB) repair, sensitizing cancer cells to ionizing radiation (IR). However, no Artemis-targeted inhibitors are currently available for therapeutic use. This study aims to identify and characterize novel small-molecule Artemis inhibitors that act as potential radiosensitizers in cancer treatment. Methods: Micronuclei formation was assessed in Artemis-deficient (CJ179), proficient (1BR3), and mutant (48BR) cell lines following 1 Gy IR exposure. Initial in vitro screening identified HMAD as a potential Artemis inhibitor. A focused virtual screening of 69 compounds was performed using AutoDock4 and Glide to evaluate binding affinity to Artemis. The top 16 compounds (ΔG < -8.0 kcal/mol) were further analyzed. Density Functional Theory (DFT) calculations at the B3LYP/6-311+G(d,p) level were used to assess frontier molecular orbitals and reactivity. ADMET profiling was conducted to evaluate pharmacokinetic properties. Compounds 42 and 51 were subjected to 100 ns molecular dynamics (MD) simulations with MMGBSA binding free energy calculations, PCA, and FEL analysis. Results: CJ179 cells exhibited significantly higher micronuclei post-irradiation, confirming Artemis's role in DNA repair. Among the top hits, compound 42 showed a highly stable binding profile, with a favorable MMGBSA binding energy of -36.94 kcal/mol. ADMET analysis indicated optimal drug-like properties. MD simulations revealed stable interaction trajectories, hydrogen bonding, and a narrow binding pocket. PCA and FEL analysis further supported the dynamic stability of compound 42. Discussion: This study identifies compound 42 as a promising Artemis inhibitor with potential as a radiosensitizing agent. The integrated
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.