ArticleJournal of the American Chemical Society2016
Development of Specific, Irreversible Inhibitors for a Receptor Tyrosine Kinase EphB3.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 36 citations in OpenAlex.
- Covalent Targeting Leads to the Development of a LIMK1 Isoform-Selective Inhibitor.Journal of medicinal chemistry · 2025Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Reactivity-based chemical-genetic study of protein kinases.RSC medicinal chemistry · 2022Review
- An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 MCell chemical biology · 2021Article
- Hit Identification of a Novel Quinazoline Sulfonamide as a Promising EphB3 Inhibitor: Design, Virtual Combinatorial Library, Synthesis, Biological Evaluation, and Docking Simulation Studies.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Barcoded viral tracing of single-cell interactions in central nervous system inflammation.Science (New York, N.Y.) · 2021Article
- Identification of tetracycline combinations as EphB1 tyrosine kinase inhibitors for treatment of neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases.Molecular cell · 2020Article
- Rigidification Dramatically Improves Inhibitor Selectivity for RAF Kinases.ACS medicinal chemistry letters · 2019Article
- Expanding the Arsenal of FGFR Inhibitors: A Novel Chloroacetamide Derivative as a New Irreversible Agent With Anti-proliferative Activity Against FGFR1-Amplified Lung Cancer Cell Lines.Frontiers in oncology · 2019Article
- Neolymphostin A Is a Covalent Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitor That Employs an Unusual Electrophilic Vinylogous Ester.Journal of medicinal chemistry · 2018Article
- Therapeutic potential of targeting the Eph/ephrin signaling complex.The international journal of biochemistry & cell biology · 2018Review
- A Chemical-Genetic Approach to Generate Selective Covalent Inhibitors of Protein Kinases.ACS chemical biology · 2017Article
- Covalent Modulators of the Vacuolar ATPase.Journal of the American Chemical Society · 2017Article
- Using Protein-Confined Proximity To Determine Chemical Reactivity.Journal of the American Chemical Society · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Erythropoietin-producing human hepatocellular carcinoma (Eph) receptor tyrosine kinases (RTKs) regulate a variety of dynamic cellular events, including cell protrusion, migration, proliferation, and cell-fate determination. Small-molecule inhibitors of Eph kinases are valuable tools for dissecting the physiological and pathological roles of Eph. However, there is a lack of small-molecule inhibitors that are selective for individual Eph isoforms due to the high homology within the family. Herein, we report the development of the first potent and specific inhibitors of a single Eph isoform, EphB3. Through structural bioinformatic analysis, we identified a cysteine in the hinge region of the EphB3 kinase domain, a feature that is not shared with any other human kinases. We synthesized and characterized a series of electrophilic quinazolines to target this unique, reactive feature in EphB3. Some of the electrophilic quinazolines selectively and potently inhibited EphB3 both in vitro and in cells. Cocrystal structures of EphB3 in complex with two quinazolines confirmed the covalent linkage between the protein and the inhibitors. A "clickable" version of an optimized inhibitor was created and employed to verify specific target engagement in the whole proteome and to probe the extent and kinetics of target engagement of existing EphB3 inhibitors. Furthermore, we demonstrate that the autophosphorylation of EphB3 within the juxtamembrane region occurs in trans using a specific inhibitor. These exquisitely specific inhibitors will facilitate the dissection of EphB3's role in various biological processes and disease contribution.
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.