Asset Details
Do you wish to reserve the book?
Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation
Do you wish to request the book?
Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation
2020
Overview
Aflibercept (AFL) is an Fc fusion protein used in the treatment of colorectal cancers and different ophthalmological diseases. There are two medicines in which AFL is the active substance: Zaltrap and Eylea, referred as ziv-AFL and AFL respectively. No proper accelerated degradation studies were published on either AFL or ziv-AFL. These studies are essential during research, development and manufacturing stages. Here, we characterized ziv-AFL and submitted it to different stress conditions: light, 60 °C, freeze-thaw cycles, changes in pH, high hypertonic solution and strong denaturing conditions. We used an array of techniques to detect aggregation (SE-HPLC/DAD and DLS), changes in secondary structure (Far-UV circular dichroism), changes in conformation or tertiary structure (Intrinsic tryptophan fluorescence) and alterations in functionality (ELISA). Results indicate that aggregation is common degradation pathway. Two different types of aggregates were detected: dimers and high molecular weight aggregates attributed to β-amyloid-like structures. Secondary structure was maintained in most of the stress tests, while conformation was altered by almost all the tests except for the freeze-thaw cycles. Functionality, evaluated by its immunochemical reaction with VEGF, was found to be stable but with decrease when exposed to light and with likely partial inactivation of the drug when pH was altered.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 82
/ 82/1
/ 82/16
/ Angiogenesis Inhibitors - chemistry
/ Angiogenesis Inhibitors - therapeutic use
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - pathology
/ Enzyme-linked immunosorbent assay
/ High-performance liquid chromatography
/ Hot Temperature - adverse effects
/ Humanities and Social Sciences
/ Humans
/ Hypertonic Solutions - adverse effects
/ Medicine
/ Proteins
/ R&D
/ Receptors, Vascular Endothelial Growth Factor - chemistry
/ Receptors, Vascular Endothelial Growth Factor - therapeutic use
/ Recombinant Fusion Proteins - chemistry
/ Recombinant Fusion Proteins - therapeutic use
/ Science
/ Vascular endothelial growth factor
