Cargando…
Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs
Cancer is the second most common cause of death in the United States, accounting for 602,350 deaths in 2020. Cancer-related death rates have declined by 27% over the past two decades, partially due to the identification of novel anti-cancer drugs. Despite improvements in cancer treatment, newly appr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227314/ https://www.ncbi.nlm.nih.gov/pubmed/35744803 http://dx.doi.org/10.3390/molecules27123678 |
_version_ | 1784734143430524928 |
---|---|
author | Beck, Tyler C. Springs, Kendra Morningstar, Jordan E. Mills, Catherine Stoddard, Andrew Guo, Lilong Moore, Kelsey Gensemer, Cortney Biggs, Rachel Petrucci, Taylor Kwon, Jennie Stayer, Kristina Koren, Natalie Dunne, Jaclyn Fulmer, Diana Vohra, Ayesha Mai, Le Dooley, Sarah Weninger, Julianna Peterson, Yuri Woster, Patrick Dix, Thomas A. Norris, Russell A. |
author_facet | Beck, Tyler C. Springs, Kendra Morningstar, Jordan E. Mills, Catherine Stoddard, Andrew Guo, Lilong Moore, Kelsey Gensemer, Cortney Biggs, Rachel Petrucci, Taylor Kwon, Jennie Stayer, Kristina Koren, Natalie Dunne, Jaclyn Fulmer, Diana Vohra, Ayesha Mai, Le Dooley, Sarah Weninger, Julianna Peterson, Yuri Woster, Patrick Dix, Thomas A. Norris, Russell A. |
author_sort | Beck, Tyler C. |
collection | PubMed |
description | Cancer is the second most common cause of death in the United States, accounting for 602,350 deaths in 2020. Cancer-related death rates have declined by 27% over the past two decades, partially due to the identification of novel anti-cancer drugs. Despite improvements in cancer treatment, newly approved oncology drugs are associated with increased toxicity risk. These toxicities may be mitigated by pharmacokinetic optimization and reductions in off-target interactions. As such, there is a need for early-stage implementation of pharmacokinetic (PK) prediction tools. Several PK prediction platforms exist, including pkCSM, SuperCypsPred, Pred-hERG, Similarity Ensemble Approach (SEA), and SwissADME. These tools can be used in screening hits, allowing for the selection of compounds were reduced toxicity and/or risk of attrition. In this short commentary, we used PK prediction tools in the optimization of mitogen activated extracellular signal-related kinase kinase 1 (MEK1) inhibitors. In doing so, we identified MEK1 inhibitors with retained activity and optimized predictive PK properties, devoid of hERG inhibition. These data support the use of publicly available PK prediction platforms in early-stage drug discovery to design safer drugs. |
format | Online Article Text |
id | pubmed-9227314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92273142022-06-25 Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs Beck, Tyler C. Springs, Kendra Morningstar, Jordan E. Mills, Catherine Stoddard, Andrew Guo, Lilong Moore, Kelsey Gensemer, Cortney Biggs, Rachel Petrucci, Taylor Kwon, Jennie Stayer, Kristina Koren, Natalie Dunne, Jaclyn Fulmer, Diana Vohra, Ayesha Mai, Le Dooley, Sarah Weninger, Julianna Peterson, Yuri Woster, Patrick Dix, Thomas A. Norris, Russell A. Molecules Communication Cancer is the second most common cause of death in the United States, accounting for 602,350 deaths in 2020. Cancer-related death rates have declined by 27% over the past two decades, partially due to the identification of novel anti-cancer drugs. Despite improvements in cancer treatment, newly approved oncology drugs are associated with increased toxicity risk. These toxicities may be mitigated by pharmacokinetic optimization and reductions in off-target interactions. As such, there is a need for early-stage implementation of pharmacokinetic (PK) prediction tools. Several PK prediction platforms exist, including pkCSM, SuperCypsPred, Pred-hERG, Similarity Ensemble Approach (SEA), and SwissADME. These tools can be used in screening hits, allowing for the selection of compounds were reduced toxicity and/or risk of attrition. In this short commentary, we used PK prediction tools in the optimization of mitogen activated extracellular signal-related kinase kinase 1 (MEK1) inhibitors. In doing so, we identified MEK1 inhibitors with retained activity and optimized predictive PK properties, devoid of hERG inhibition. These data support the use of publicly available PK prediction platforms in early-stage drug discovery to design safer drugs. MDPI 2022-06-08 /pmc/articles/PMC9227314/ /pubmed/35744803 http://dx.doi.org/10.3390/molecules27123678 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Beck, Tyler C. Springs, Kendra Morningstar, Jordan E. Mills, Catherine Stoddard, Andrew Guo, Lilong Moore, Kelsey Gensemer, Cortney Biggs, Rachel Petrucci, Taylor Kwon, Jennie Stayer, Kristina Koren, Natalie Dunne, Jaclyn Fulmer, Diana Vohra, Ayesha Mai, Le Dooley, Sarah Weninger, Julianna Peterson, Yuri Woster, Patrick Dix, Thomas A. Norris, Russell A. Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs |
title | Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs |
title_full | Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs |
title_fullStr | Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs |
title_full_unstemmed | Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs |
title_short | Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs |
title_sort | application of pharmacokinetic prediction platforms in the design of optimized anti-cancer drugs |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227314/ https://www.ncbi.nlm.nih.gov/pubmed/35744803 http://dx.doi.org/10.3390/molecules27123678 |
work_keys_str_mv | AT becktylerc applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT springskendra applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT morningstarjordane applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT millscatherine applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT stoddardandrew applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT guolilong applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT moorekelsey applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT gensemercortney applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT biggsrachel applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT petruccitaylor applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT kwonjennie applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT stayerkristina applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT korennatalie applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT dunnejaclyn applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT fulmerdiana applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT vohraayesha applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT maile applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT dooleysarah applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT weningerjulianna applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT petersonyuri applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT wosterpatrick applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT dixthomasa applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs AT norrisrussella applicationofpharmacokineticpredictionplatformsinthedesignofoptimizedanticancerdrugs |