ArticleJournal of medicinal chemistry2008
Substitution of aminomethyl at the meta-position enhances the inactivation of O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine.
Article in Journal of medicinal chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 31 citations in OpenAlex.
- The Versatile Attributes of MGMT: Its Repair Mechanism, Crosstalk with Other DNA Repair Pathways, and Its Role in Cancer.Cancers · 2024Review
- QSAR and Chemical Read-Across Analysis of 370 Potential MGMT Inactivators to Identify the Structural Features Influencing Inactivation Potency.Pharmaceutics · 2023Article
- Proteome-Wide Profiling of the Covalent-Druggable Cysteines with a Structure-Based Deep Graph Learning Network.Research (Washington, D.C.) · 2022Article
- Reductive Activity and Mechanism of Hypoxia- Targeted AGT Inhibitors: An Experimental and Theoretical Investigation.International journal of molecular sciences · 2019Article
- In Silico Prediction of O⁶-Methylguanine-DNA Methyltransferase Inhibitory Potency of Base Analogs with QSAR and Machine Learning Methods.Molecules (Basel, Switzerland) · 2018Article
- Elucidating a chemical defense mechanism of Antarctic sponges: A computational study.Journal of molecular graphics & modelling · 2017Article
- Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking.Molecules (Basel, Switzerland) · 2016Article
- Design of a hypoxia-activated prodrug inhibitor of O6-alkylguanine-DNA alkyltransferase.Bioorganic & medicinal chemistry letters · 2012Article
- Virtual target screening: validation using kinase inhibitors.Journal of chemical information and modeling · 2012Article
- Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools.Chemical research in toxicology · 2011Review
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
O(6)-Benzylguanine is an irreversible inactivator of O(6)-alkylguanine-DNA alkyltransferase currently in clinical trials to overcome alkyltransferase-mediated resistance to certain cancer chemotherapeutic alkylating agents. In order to produce more soluble alkyltransferase inhibitors, we have synthesized three aminomethyl-substituted O(6)-benzylguanines and the three methyl analogs and found that the substitution of aminomethyl at the meta-position greatly enhances inactivation of alkyltransferase, whereas para-substitution has little effect and ortho-substitution virtually eliminates activity. Molecular modeling of their interactions with alkyltransferase provided a molecular explanation for these results. The square of the correlation coefficient (R(2)) obtained between E-model scores (obtained from GLIDE XP/QPLD docking calculations) vs log(ED(50)) values via a linear regression analysis was 0.96. The models indicate that the ortho-substitution causes a steric clash interfering with binding, whereas the meta-aminomethyl substitution allows an interaction of the amino group to generate an additional hydrogen bond with the protein.
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.