ArticleEuropean journal of medicinal chemistry2016
The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity.
Article in European journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 38 citations in OpenAlex.
- In Silico Studies of Potent Tyrosine Kinase Inhibitors: Molecular Docking and Pharmacophore Modeling Approaches.Molecules (Basel, Switzerland) · 2026Article
- Using a Novel Consensus-Based Chemoinformatics Approach to Predict ADMET Properties and Druglikeness of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2025Review
- Role of heterocycles in inhibition of VEGFR-2 - a recent update (2019-2022).RSC medicinal chemistry · 2024Review
- Design, synthesis, docking, ADMET and anticancer evaluations ofRSC advances · 2023Article
- Design and Synthesis of Novel Thieno[3,2-ACS omega · 2023Article
- Efficacy and Tolerability of Pyrazolo[1,5-ACS medicinal chemistry letters · 2020Article
- Precision medicine for ovarian clear cell carcinoma based on gene alterations.International journal of clinical oncology · 2020Review
- Synthesis of Mono-ACS omega · 2019Article
- The molecular basis for RET tyrosine-kinase inhibitors in thyroid cancer.Best practice & research. Clinical endocrinology & metabolism · 2017Review
- Anilinoquinazoline inhibitors of the RET kinase domain-Elaboration of the 7-position.Bioorganic & medicinal chemistry letters · 2016Article
- Identification of selective inhibitors of RET and comparison with current clinical candidates through development and validation of a robust screening cascade.F1000Research · 2016Article
Corrections and comments
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Authors and funding
25 authors at 3 institutions in 1 country.
Funding
Abstract
Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clinically approved multi-kinase inhibitors that target RET as a secondary pharmacology but additional activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clinical need for more specific RET kinase inhibitors. Herein we report our efforts towards identifying a potent and selective RET inhibitor using vandetanib 1 as the starting point for structure-based drug design. Phenolic anilinoquinazolines exemplified by 6 showed improved affinities towards RET but, unsurprisingly, suffered from high metabolic clearance. Efforts to mitigate the metabolic liability of the phenol led to the discovery that a flanking substituent not only improved the hepatocyte stability, but could also impart a significant gain in selectivity. This culminated in the identification of 36; a potent RET inhibitor with much improved selectivity against KDR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.