دورية أكاديمية
Knockout mouse models are predictive of malformations or embryo-fetal death in drug safety evaluations.
| العنوان: | Knockout mouse models are predictive of malformations or embryo-fetal death in drug safety evaluations. |
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| المؤلفون: | Catlin NR; Pfizer, Inc., Groton, CT, USA. Electronic address: natasha.catlin@pfizer.com., Stethem C; Pfizer, Inc., Groton, CT, USA., Bowman CJ; Pfizer, Inc., Groton, CT, USA., Campion SN; Pfizer, Inc., Groton, CT, USA., Nowland WS; Pfizer, Inc., Groton, CT, USA., Cappon GD; Pfizer, Inc., Groton, CT, USA. |
| المصدر: | Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2021 Jan; Vol. 99, pp. 138-143. Date of Electronic Publication: 2020 Oct 13. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon In Cooperation With The Reproductive Toxicology Center Country of Publication: United States NLM ID: 8803591 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-1708 (Electronic) Linking ISSN: 08906238 NLM ISO Abbreviation: Reprod Toxicol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Elmsford Ny : Pergamon In Cooperation With The Reproductive Toxicology Center Original Publication: Elmsford, N.Y., U.S.A. : Pergamon Press, c1987- |
| مواضيع طبية MeSH: | Abnormalities, Drug-Induced* , Models, Animal*, Drug Evaluation, Preclinical/*methods , Teratogens/*toxicity, Animals ; Embryo, Mammalian/drug effects ; Fetal Death/etiology ; Mice, Knockout ; Mice |
| مستخلص: | Traditionally, understanding potential developmental toxicity from pharmaceutical exposures has been based on the results of ICH guideline studies in two species. However, support is growing for the use of weight of evidence approaches when communicating the risk of developmental toxicity, where the intended pharmacologic mode of action affects fundamental pathways in developmental biology or phenotypic data from genetically modified animals may increasingly be included in the overall assessment. Since some concern surrounds the use of data from knockout (KO) mice to accurately predict the risk for pharmaceutical modulation of a target, a deeper understanding of the relevance and predictivity of adverse developmental effects in KO mice for pharmacological target modulation is needed. To this end, we compared the results of embryo-fetal development (EFD) studies for 86 drugs approved by the FDA from 2017 to 2019 that also had KO mouse data available in the public domain. These comparisons demonstrate that data from KO mouse models are overall highly predictive of malformations or embryo-fetal lethality (MEFL) from EFD studies, but less so of a negative outcome in EFD studies. This information supports the use of embryo-fetal toxicity data in KO models as part of weight of evidence approaches in the communication of developmental toxicity risk of pharmaceutical compounds. Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: (Copyright © 2020. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Developmental toxicity; Knockout mice; Nonclinical data; Prediction; Transgenic mice |
| المشرفين على المادة: | 0 (Teratogens) |
| تواريخ الأحداث: | Date Created: 20201016 Date Completed: 20211112 Latest Revision: 20240226 |
| رمز التحديث: | 20240226 |
| DOI: | 10.1016/j.reprotox.2020.10.002 |
| PMID: | 33065206 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-1708 |
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| DOI: | 10.1016/j.reprotox.2020.10.002 |