1. Design, synthesis and biological evaluation of novel aminopyrazole- and 7-azaindole-based Nek1 inhibitors and their effects on zebrafish kidney development.
- Author
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Pilakowski J, Baumann G, Shih YH, Meckel T, and Schmidt B
- Subjects
- Animals, Dose-Response Relationship, Drug, Indoles chemical synthesis, Indoles chemistry, Kidney growth & development, Kidney metabolism, Molecular Structure, NIMA-Related Kinase 1 metabolism, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Pyrazoles chemical synthesis, Pyrazoles chemistry, Structure-Activity Relationship, Zebrafish, Drug Design, Indoles pharmacology, Kidney drug effects, NIMA-Related Kinase 1 antagonists & inhibitors, Protein Kinase Inhibitors pharmacology, Pyrazoles pharmacology
- Abstract
NIMA-related protein kinase Nek1 is crucially involved in cell cycle regulation, DNA repair and microtubule regulation and dysfunctions of Nek1 play key roles in amyotrophic lateral sclerosis (ALS), polycystic kidney disease (PKD) and several types of radiotherapy resistant cancer. Targeting of Nek1 could reveal a new class of radiosensitizing substances and provide useful tools to better understand the aforementioned diseases. In this report we explore substituted aminopyrazoles and 7-azaindoles as potent inhibitors for the Nek1 kinase domain and examine their effect on kidney organogenesis in Danio rerio., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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