Design, synthesis and biological evaluation of novel aminopyrazole- and 7-azaindole-based Nek1 inhibitors and their effects on zebrafish kidney development.

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.

• Authors: Johannes Pilakowski, Georg Baumann, Yung-Hsin Shih, Tobias Meckel, Boris Schmidt
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 53 Pg. 128418 (12 01 2021) ISSN: 1464-3405 [Electronic] England
• PMID: 34715306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• 7-azaindole dimer
• Indoles
• Protein Kinase Inhibitors
• Pyrazoles
• NIMA-Related Kinase 1

Topics

• Animals
• Dose-Response Relationship, Drug
• Drug Design
• Indoles (chemical synthesis, chemistry, pharmacology)
• Kidney (drug effects, growth & development, metabolism)
• Molecular Structure
• NIMA-Related Kinase 1 (antagonists & inhibitors, metabolism)
• Protein Kinase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Pyrazoles (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Zebrafish