ArticleInternational journal of molecular sciences2022
In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part I.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 10 citations in OpenAlex.
- Article
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- Feeding aAnimals : an open access journal from MDPI · 2024Article
- Novel Strategies in the Development of New Therapies, Drug Substances, and Drug Carriers Volume II.International journal of molecular sciences · 2023Article
- In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part III.International journal of molecular sciences · 2023Article
- In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part I.International journal of molecular sciences · 2022Article
- In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part II.International journal of molecular sciences · 2022Article
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 3 institutions in 2 countries.
Funding
Abstract
Translation of the synergy between the Siremadlin (MDM2 inhibitor) and Trametinib (MEK inhibitor) combination observed in vitro into in vivo synergistic efficacy in melanoma requires estimation of the interaction between these molecules at the pharmacokinetic (PK) and pharmacodynamic (PD) levels. The cytotoxicity of the Siremadlin and Trametinib combination was evaluated in vitro in melanoma A375 cells with MTS and RealTime-Glo assays. Analysis of the drug combination matrix was performed using Synergy and Synergyfinder packages. Calculated drug interaction metrics showed high synergy between Siremadlin and Trametinib: 23.12%, or a 7.48% increase of combined drug efficacy (concentration-independent parameter β from Synergy package analysis and concentration-dependent δ parameter from Synergyfinder analysis, respectively). In order to select the optimal PD interaction parameter which may translate observed in vitro synergy metrics into the in vivo setting, further PK/PD studies on cancer xenograft animal models coupled with PBPK/PD modelling are needed.
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.