ArticleEuropean biophysics journal : EBJ2019
Electrostatic mechanism of V600E mutation-induced B-Raf constitutive activation in colorectal cancer: molecular implications for the selectivity difference between type-I and type-II inhibitors.
Article in European biophysics journal : EBJ, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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
7 citing papers in PubMed, 14 citations in OpenAlex.
- Antitumor effects of CEP32496 on urothelial carcinoma with BRAF mutation (V595E) in dogs.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2026Article
- Review
- Recent advances of anti-angiogenic inhibitors targeting VEGF/VEGFR axis.Frontiers in pharmacology · 2023Review
- Coincidence of v-raf murine sarcoma viral oncogene homolog B mutation (V595E) with phosphorylated v-raf murine sarcoma viral oncogene homolog B in urothelial carcinoma in dogs.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2022Article
- Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.Signal transduction and targeted therapy · 2021Review
- Low immunogenicity of common cancer hot spot mutations resulting in false immunogenic selection signals.PLoS genetics · 2021Article
- Electrostatic explanation of D1228V/H/N-induced c-Met resistance and sensitivity to type I and type II kinase inhibitors in targeted gastric cancer therapy.Journal of molecular modeling · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The oncogenic mutation V600E in B-Raf activation loop (A-loop) has been frequently observed to cause drug resistance in colorectal cancer chemotherapy. Here, the molecular mechanism of V600E-induced conformational flipping of B-Raf activation loop (A-loop) is investigated systematically via continuum electrostatic analysis. It is found that substitution of the electroneutral Val600 residue with negatively charged glutamic acid Glu600 electrostatically destabilizes the inactive DFG-out conformation of B-Raf kinase and promotes its shifting to active DFG-in conformation. This is analogous with natural phosphorylation of Thr598 and/or Ser601 residues in A-loop to activate the kinase, that is, both the mutation and phosphorylation can introduce negative charge to B-Raf A-loop and then trigger the loop flipping. Energetic analysis reveals that the V600E mutation can affect inhibitor binding indirectly via regulation of kinase conformation. Type-I and type-II inhibitors respond distinctly to V600E mutation; the former is sensitized by the mutation, while the latter generally shows a low sensitivity to the mutation. Based on this guideline, the sophisticated type-I pan-kinase inhibitor Staurosporine as well as its analogs Midostaurin and Lestaurtinib are identified as potent mutant-selective inhibitors by modeling analysis and kinase assay, which exhibit a moderate or high selectivity for B-Raf
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.