ArticlePharmaceuticals (Basel, Switzerland)2014
The medicinal chemistry of imidazotetrazine prodrugs.
Article in Pharmaceuticals (Basel, Switzerland), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed.
- E3 ligase LMO7 enhances temozolomide sensitivity by promoting MGMT degradation in lung cancer.The Journal of biological chemistry · 2026Article
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- USP7 promotes temozolomide resistance by stabilizing MGMT in glioblastoma.Cell death & disease · 2025Article
- Establishment of U-87MG Cellular Fibrosis as a Novel in Vitro Model to Analyze Glioblastoma Cells' Sensitivity to Temozolomide.International journal of molecular sciences · 2025Article
- GNE-317 Reverses MSN-Mediated Proneural-to-Mesenchymal Transition and Suppresses Chemoradiotherapy Resistance in Glioblastoma via PI3K/mTOR.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DDX3X dynamics, glioblastoma's genetic landscape, therapeutic advances, and autophagic interplay.Medical oncology (Northwood, London, England) · 2024Review
- Dual-Action Therapeutics: DNA Alkylation and Antimicrobial Peptides for Cancer Therapy.Cancers · 2024Review
- Boric acid Increases Susceptibility to Chemotherapy by Targeting the Ferritinophagy Signaling Pathway in TMZ Resistant Glioblastoma Cells.Biological trace element research · 2024Article
- Mechanism of Action of KL-50, a Candidate Imidazotetrazine for the Treatment of Drug-Resistant Brain Cancers.Journal of the American Chemical Society · 2024Article
- Article
- The Synthesis and Characterization of a Delivery System Based on Polymersomes and a Xanthone with Inhibitory Activity in Glioblastoma.Life (Basel, Switzerland) · 2024Article
- Polymersomes for Sustained Delivery of a Chalcone Derivative Targeting Glioblastoma Cells.Brain sciences · 2024Article
- Systemic and local immunosuppression in glioblastoma and its prognostic significance.Frontiers in immunology · 2024Review
- An anti-depressant drug vortioxetine suppresses malignant glioblastoma cell growth.microPublication biology · 2024Article
- Article
- Antitumour imidazotetrazines: past, present… and future?RSC chemical biology · 2023Review
- Identification of the E2F1-RAD51AP1 axis as a key factor in MGMT-methylated GBM TMZ resistance.Cancer biology & medicine · 2023Article
- A receptor-mediated landscape of druggable and targeted nanomaterials for gliomas.Materials today. Bio · 2023Review
- The effect of Azo-dyes on glioblastoma cellsSaudi journal of biological sciences · 2023Article
- Exploring the Use of Cold Atmospheric Plasma to Overcome Drug Resistance in Cancer.Biomedicines · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temozolomide (TMZ) is the standard first line treatment for malignant glioma, reaching "blockbuster" status in 2010, yet it remains the only drug in its class. The main constraints on the clinical effectiveness of TMZ therapy are its requirement for active DNA mismatch repair (MMR) proteins for activity, and inherent resistance through O6-methyl guanine-DNA methyl transferase (MGMT) activity. Moreover, acquired resistance, due to MMR mutation, results in aggressive TMZ-resistant tumour regrowth following good initial responses. Much of the attraction in TMZ as a drug lies in its PK/PD properties: it is acid stable and has 100% oral bioavailability; it also has excellent distribution properties, crosses the blood-brain barrier, and there is direct evidence of tumour localisation. This review seeks to unravel some of the mysteries of the imidazotetrazine class of compounds to which TMZ belongs. In addition to an overview of different synthetic strategies, we explore the somewhat unusual chemical reactivity of the imidazotetrazines, probing their mechanisms of reaction, examining which attributes are required for an active drug molecule and reviewing the use of this combined knowledge towards the development of new and improved anti-cancer agents.
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.