ArticleJournal of medicinal chemistry2013
Pseudo-cyclization through intramolecular hydrogen bond enables discovery of pyridine substituted pyrimidines as new Mer kinase inhibitors.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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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.
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Who cites it
31 citing papers in PubMed, 69 citations in OpenAlex.
- MERTK coordinates efferocytosis by regulating integrin localization and activation.Journal of cell science · 2026Article
- Discovery of Novel 2-Substituted Aniline Pyrimidine Based Derivatives as Potent Mer/c-Met Dual Inhibitors with Improvement Bioavailability.Biomolecules · 2025Article
- Exploiting structural variability in the kinase back-pocket to modulate polypharmacology of TAM inhibitors.European journal of medicinal chemistry · 2025Article
- Discovery of Novel TYRO3/MERTK Dual Inhibitors.Journal of medicinal chemistry · 2025Article
- UNC9426, a Potent and Orally Bioavailable TYRO3-Specific Inhibitor.Journal of medicinal chemistry · 2025Article
- Advances in reversible covalent kinase inhibitors.Medicinal research reviews · 2025Review
- Design, Synthesis, and Biological Evaluation of 3-Amino-pyrazine-2-carboxamide Derivatives as Novel FGFR Inhibitors.ACS medicinal chemistry letters · 2024Article
- Discovery of Novel Macrocyclic MERTK/AXL Dual Inhibitors.Journal of medicinal chemistry · 2024Article
- Design, Synthesis, and Biological Evaluation of 2-Substituted Aniline Pyrimidine Derivatives as Potent Dual Mer/c-Met Inhibitors.Molecules (Basel, Switzerland) · 2024Article
- TYRO3 blockade enhances anti-PD-1 therapy response by modulating expression of CCN1 in tumor microenvironment.Journal for immunotherapy of cancer · 2023Article
- BMS794833 inhibits macrophage efferocytosis by directly binding to MERTK and inhibiting its activity.Experimental & molecular medicine · 2022Article
- Review
- MERTK Inhibition: Potential as a Treatment Strategy in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Crystal Structure of the Kinase Domain of MerTK in Complex with AZD7762 Provides Clues for Structure-Based Drug Development.International journal of molecular sciences · 2020Article
- MERTK in cancer therapy: Targeting the receptor tyrosine kinase in tumor cells and the immune system.Pharmacology & therapeutics · 2020Review
- Data-Driven Construction of Antitumor Agents with Controlled Polypharmacology.Journal of the American Chemical Society · 2019Article
- A critical role of the Gas6-Mer axis in endothelial dysfunction contributing to TA-TMA associated with GVHD.Blood advances · 2019Article
- Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment.Molecular cancer · 2019Review
- TYRO3: A potential therapeutic target in cancer.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Abnormal activation or overexpression of Mer receptor tyrosine kinase has been implicated in survival signaling and chemoresistance in many human cancers. Consequently, Mer is a promising novel cancer therapeutic target. A structure-based drug design approach using a pseudo-ring replacement strategy was developed and validated to discover a new family of pyridinepyrimidine analogues as potent Mer inhibitors. Through SAR studies, 10 (UNC2250) was identified as the lead compound for further investigation based on high selectivity against other kinases and good pharmacokinetic properties. When applied to live cells, 10 inhibited steady-state phosphorylation of endogenous Mer with an IC50 of 9.8 nM and blocked ligand-stimulated activation of a chimeric EGFR-Mer protein. Treatment with 10 also resulted in decreased colony-forming potential in rhabdoid and NSCLC tumor cells, thereby demonstrating functional antitumor activity. The results provide a rationale for further investigation of this compound for therapeutic application in patients with cancer.
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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.