ArticleChemMedChem2017
Discovery of Macrocyclic Pyrimidines as MerTK-Specific Inhibitors.
Article in ChemMedChem, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed.
- Mesenchymal stem cell-derived exosome delivery of let-7a-5p enhances macrophage efferocytosis via Arid3a/Mertk axis in acute-on-chronic liver failure.Stem cells translational medicine · 2025Article
- From pathogenesis to therapeutic targeting: new insight into TAM receptors in rheumatoid arthritis.Cell & bioscience · 2025Review
- Enhancing Chemosensitivity With Quercetin: Mechanistic Insights Into MerTK and Associated Signaling Pathways.Cancer reports (Hoboken, N.J.) · 2025Review
- Exploiting structural variability in the kinase back-pocket to modulate polypharmacology of TAM inhibitors.European journal of medicinal chemistry · 2025Article
- UNC9426, a Potent and Orally Bioavailable TYRO3-Specific Inhibitor.Journal of medicinal chemistry · 2025Article
- Discovery of Novel Macrocyclic MERTK/AXL Dual Inhibitors.Journal of medicinal chemistry · 2024Article
- Rigid Scaffolds Are Promising for Designing Macrocyclic Kinase Inhibitors.ACS pharmacology & translational science · 2023Article
- BMS794833 inhibits macrophage efferocytosis by directly binding to MERTK and inhibiting its activity.Experimental & molecular medicine · 2022Article
- Review
- The Synthesis and Initial Evaluation of MerTK Targeted PET Agents.Molecules (Basel, Switzerland) · 2022Article
- 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
- Synthesis and Characterization of a Click-Assembled 18-Atom Macrocycle That Displays Selective AXL Kinase Inhibitory Activity.ACS omega · 2019Article
- Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment.Molecular cancer · 2019Review
- MERTK tyrosine kinase receptor together with TIM4 phosphatidylserine receptor mediates distinct signal transduction pathways for efferocytosis and cell proliferation.The Journal of biological chemistry · 2019Article
- ICBS 2017 in Shanghai-Illuminating Life with Chemical Innovation.ACS chemical biology · 2018Article
- The small-molecule MERTK inhibitor UNC2025 decreases platelet activation and prevents thrombosis.Journal of thrombosis and haemostasis : JTH · 2018Article
- Dual targeting of TAM receptors Tyro3, Axl, and MerTK: Role in tumors and the tumor immune microenvironment.Tzu chi medical journalReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
Macrocycles have attracted significant attention in drug discovery recently. In fact, a few de novo designed macrocyclic kinase inhibitors are currently in clinical trials with good potency and selectivity for their intended target. In this study, we successfully engaged a structure-based drug design approach to discover macrocyclic pyrimidines as potent Mer tyrosine kinase (MerTK)-specific inhibitors. An enzyme-linked immunosorbent assay (ELISA) in 384-well format was employed to evaluate the inhibitory activity of macrocycles in a cell-based assay assessing tyrosine phosphorylation of MerTK. Through structure-activity relationship (SAR) studies, analogue 11 [UNC2541; (S)-7-amino-N-(4-fluorobenzyl)-8-oxo-2,9,16-triaza-1(2,4)-pyrimidinacyclohexadecaphane-1-carboxamide] was identified as a potent and MerTK-specific inhibitor that exhibits sub-micromolar inhibitory activity in the cell-based ELISA. In addition, an X-ray structure of MerTK protein in complex with 11 was resolved to show that these macrocycles bind in the MerTK ATP pocket.
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.