Drug Responses in Plexiform Neurofibroma Type I (PNF1) Cell Lines Using High-Throughput Data and Combined Effectiveness and Potency
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines, Data Access, and Extraction
2.2. Data Analysis
2.2.1. AC50 (Potency) and Relative Potency
2.2.2. The S and ΔS Indices
2.2.3. Prioritization
2.2.4. Reference Cell Line and Use of Alternate and Multiple Controls
3. Results
3.1. Drug Resistance and Sensitivity Focusing Primarily on a Single PNF1 Cell Line
3.2. Drug Assessment by Signaling Pathway
3.3. Discussion of Prioritized Compounds
3.3.1. MEK Inhibitors
3.3.2. PI3K and AKT1 Inhibitors
3.3.3. TOP2A and CHEK1 Gene Product Inhibitors
3.3.4. Heat Shock Proteins
3.3.5. Serotonin Modulators
3.3.6. Non-Prioritized Compounds of Interest
3.4. Comparing Ranking Methodologies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Human Cell Lines | |||
---|---|---|---|
Cell Line | Immortalized | Tissue Source | Neurofibromin Status |
ipnNF95.11C * | yes | Peripheral nerve (non-tumor) | +/− |
ipNF06.2A | yes | Plexiform Neurofibroma (PNF1) | −/− |
ipNF95.6 * | yes | Plexiform Neurofibroma (PNF1) | −/− |
ipNF95.11b C/T | yes | Plexiform Neurofibroma (PNF1) | −/− |
ipNF05.5 Mixed Clone (ipNF05.5-MX) | yes | Plexiform Neurofibroma (PNF1) | −/− |
PI3KCA | AKT1 | MTOR | ||||||
---|---|---|---|---|---|---|---|---|
Compound | ΔS Mean | ΔS Variance | Compound | ΔS Mean | ΔS Variance | Compound | ΔS Mean | ΔS Variance |
GNE-490 | −0.66 | 0.25 | Triciribine-PO4 | −1.51 | 0.81 | WYE-354 | −0.53 | 1.15 |
NIBR-17 | −0.48 | 0.14 | A-443654 | −0.82 | 0.04 | AZD-2014 | −0.34 | 0.24 |
PIK-90 | −0.45 | 0.01 | AT-7867 | −0.62 | 0.16 | GDC-0980 | −0.24 | 0.14 |
BKM-120 | −0.33 | 0.47 | AZD-5363 | −0.36 | 0.10 | KU-0063794 | −0.23 | 0.04 |
PF-04691502 | −0.31 | 0.20 | GDC-0068 | −0.34 | 0.12 | AZD-8055 | −0.22 | 0.38 |
GNE-493 | −0.28 | 0.08 | H-89 | −0.26 | 0.12 | WAY-600 | −0.20 | 0.19 |
PIK-93 | −0.28 | 0.23 | MK-2206 | −0.13 | 0.02 | PP-242 | −0.20 | 0.89 |
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Zamora, P.O.; Altay, G.; Santamaria, U.; Dwarshuis, N.; Donthi, H.; Moon, C.I.; Bakalar, D.; Zamora, M. Drug Responses in Plexiform Neurofibroma Type I (PNF1) Cell Lines Using High-Throughput Data and Combined Effectiveness and Potency. Cancers 2023, 15, 5811. https://doi.org/10.3390/cancers15245811
Zamora PO, Altay G, Santamaria U, Dwarshuis N, Donthi H, Moon CI, Bakalar D, Zamora M. Drug Responses in Plexiform Neurofibroma Type I (PNF1) Cell Lines Using High-Throughput Data and Combined Effectiveness and Potency. Cancers. 2023; 15(24):5811. https://doi.org/10.3390/cancers15245811
Chicago/Turabian StyleZamora, Paul O., Gabriel Altay, Ulisses Santamaria, Nathan Dwarshuis, Hari Donthi, Chang In Moon, Dana Bakalar, and Matthew Zamora. 2023. "Drug Responses in Plexiform Neurofibroma Type I (PNF1) Cell Lines Using High-Throughput Data and Combined Effectiveness and Potency" Cancers 15, no. 24: 5811. https://doi.org/10.3390/cancers15245811