ArticleACS chemical biology2019
Leveraging Atropisomerism to Obtain a Selective Inhibitor of RET Kinase with Secondary Activities toward EGFR Mutants.
Article in ACS chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- A Rh(II) Catalyzed Atropisomer Selective Ring Expansion of 3-Aryl Indoles to 4-Aryl Quinolines.ACS catalysis · 2026Article
- Fourth-generation EGFR-TKI to overcome C797S mutation: past, present, and future.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Synthetic, Computational, and Experimental Studies of a Class 3 Atropisomeric α-Naphthyl Tropone.The Journal of organic chemistry · 2025Article
- Deconstruction of Desacetamidocolchicine's B Ring Reveals a Class 3 Atropisomeric AC Ring with Tubulin Binding Properties.The Journal of organic chemistry · 2025Article
- Studies on the Configurational Stability of Tropolone-Ketone-, Ester-, and Aldehyde-Based Chiral Axes.The Journal of organic chemistry · 2024Article
- Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy.Biochemical pharmacology · 2023Review
- Controlling Ibrutinib's Conformations about Its Heterobiaryl Axis to Increase BTK Selectivity.ACS medicinal chemistry letters · 2023Article
- Atropisomerism in the Pharmaceutically Relevant Realm.Accounts of chemical research · 2022Article
- Approaches toward Atropisomerically Stable and Conformationally Pure Diarylamines.The Journal of organic chemistry · 2022Article
- Catalytic atroposelective dynamic kinetic resolutions and kinetic resolutions towards 3-arylquinolinesChemical communications (Cambridge, England) · 2021Article
- Catalytic Atroposelective Synthesis ofJournal of the American Chemical Society · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Unstable atropisomerism is innate in many common scaffolds in drug discovery, commonly existing as freely rotating aryl-aryl bonds. Such compounds can access the majority of dihedral conformations around the bond axis; however, most small molecules bind their target within a narrow range of these available conformations. The remaining accessible conformations can interact with other proteins leading to compound promiscuity. Herein, we leverage atropisomerism to restrict the accessible low-energy dihedral conformations available to a promiscuous kinase inhibitor and achieve highly selective and potent inhibitors of the oncogenic target rearranged during transfection (RET) kinase. We then evaluate our lead inhibitor against kinases that were predicted to bind compounds in a similar conformational window to RET, discovering a potent inhibitor of drug-resistant epidermal growth factor receptor (EGFR) mutants including L858R/T790M/C797S EGFR. Leveraging atropisomerism to restrict accessible conformational space should be a generally applicable strategy due to the prevalence of unstable atropisomerism in drug discovery.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.