ArticleBiochemical pharmacology2008
Differential inactivation of polymorphic variants of human O6-alkylguanine-DNA alkyltransferase.
Article in Biochemical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed.
- Clinical and genetic predictors of temozolomide-induced severe myelotoxicity in adult diffuse glioma: a case-control study.Journal of neuro-oncology · 2026Article
- Temozolomide-induced myelotoxicity and single nucleotide polymorphisms in the MGMT gene in patients with adult diffuse glioma: a single-institutional pharmacogenetic study.Journal of neuro-oncology · 2022Article
- Blocking MAPK/ERK pathway sensitizes hepatocellular carcinoma cells to temozolomide via downregulating MGMT expression.Annals of translational medicine · 2020Article
- Impact of rs12917 MGMT Polymorphism on [Molecular imaging and biology · 2019Article
- Tumor-associated mutations in O⁶ -methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality.Molecular carcinogenesis · 2014Article
- Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools.Chemical research in toxicology · 2011Review
- In vitro comparison of O4-benzylfolate modulated, BCNU-induced toxicity in human bone marrow using CFU-GM and tumor cell lines.Cancer chemotherapy and pharmacology · 2010Article
- Repair of O4-alkylthymine by O6-alkylguanine-DNA alkyltransferases.The Journal of biological chemistry · 2010Article
- The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity.Neuro-oncology · 2009Article
- Substitution of aminomethyl at the meta-position enhances the inactivation of O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine.Journal of medicinal chemistry · 2008Article
- Repair of O6-G-alkyl-O6-G interstrand cross-links by human O6-alkylguanine-DNA alkyltransferase.Biochemistry · 2008Article
- Human variants of O6-alkylguanine-DNA alkyltransferase.DNA repair · 2007Review
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.
Funding
Abstract
The human DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (hAGT) is an important source of resistance to some therapeutic alkylating agents and attempts to circumvent this resistance by the use of hAGT inhibitors have reached clinical trials. Several human polymorphisms in the MGMT gene that encodes hAGT have been described including L84F and the linked double alteration I143V/K178R. We have investigated the inactivation of these variants and the much rarer variant W65C by O(6)-benzylguanine, which is currently in clinical trials, and a number of other second generation hAGT inhibitors that contain folate derivatives (O(4)-benzylfolic acid, the 3' and 5' folate esters of O(6)-benzyl-2'-deoxyguanosine and the folic acid gamma ester of O(6)-(p-hydroxymethyl)benzylguanine). The I143V/K178R variant was resistant to all of these compounds. The resistance was due solely to the I143V change. These results suggest that the frequency of the I143V/K178R variant among patients in the clinical trials with hAGT inhibitors and the correlation with response should be considered.
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.