In silico tailored inhibitor collection for MERTK
We provide a curated in silico collection of synthetically accessible molecules designed via machine learning/docking for MERTK, ready for synthesis and experimental validation.
| Approved Symbol | MERTK |
| Approved Name | Tyrosine-protein kinase Mer |
| Alternative Names | Proto-oncogene c-Mer /
Receptor tyrosine kinase MerTK |
| Protein Family / Class | Receptor Tyrosine Kinase – TAM family (Tyro3, AXL, MERTK) |
| UniProt | Q12866 |
Tyrosine-Protein Kinase Mer (MERTK)
Why MERTK?
MERTK is a Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands. Regulates many physiological processes, including cell survival, migration, differentiation, and phagocytosis of apoptotic cells.
It acts as an innate immune checkpoint in macrophages, exploited by cancer cells to suppress anti-tumor responses. Kinase activation triggers efferocytosis, which clears apoptotic cells without inflammation, limiting DAMP release and pro-inflammatory signaling. This process also increases PD-L1 on macrophages, suppressing T cell activation and impairing antigen presentation, thereby weakening CD4⁺ and CD8⁺ responses against tumors.
No approved drugs yet, but multiple first-in-human trials demonstrate MERTK’s high translational potential. It has high therapeutic druggability, well-suited for small-molecule intervention due to defined kinase activity and accessible binding domains.
Open-source information reinforces the attractiveness of MERTK as a therapeutic target. In PubChem, there are dozens of bioassays where MERTK appears in kinase selectivity panels. These assays provide quantitative binding and inhibition data and allow comparison of selectivity profiles across hundreds of related kinases. Currently, 339 PubChem bioassays include MERTK, with 7061 compounds tested.
In parallel, the intellectual property landscape is broad: there are over 1700 patent families covering MERTK inhibitors, including small molecules, blocking antibodies, and antibody-drug conjugates (ADCs). These filings span oncology and immunology, highlighting an active and competitive innovation ecosystem.
In short, the public data shows that MERTK is not only a clinically validated target but also one with abundant experimental evidence and strong IP protection, which both accelerates and challenges the development of new therapies.
What we built
Tailored chemical collection for MERTK, optimized with multi-objective design (predicted activity, ADMET, synthesizability, novelty).
| In silico MERTK inhibitors collection: designed to balance novelty and synthesizability | |
| Chemical Collection Size | 847 |
| Number of unique molecular seriesa | 24 |
| Minimum Number of Molecules per serie | 5 |
| Number of Unique Scaffoldsb | 426 |
| Max Similarity to Known MERTK Inhibitorsc | 0.37 |
| Intra-Collection Pairwise Similarityc | 0.29 |
| Max Synthesizability Score | 5.4 |
aNumber of molecular series determined by HCA (Tanimoto ECFP4 > 0.7)
bNumber determined as unique Bermis-Murcko Scaffold
cTanimoto Similarity Coefficient ECFP4
Molecular Properties Distribution
Predicted Tox Profile: Designed to minimize key toxicity liabilities
| No hERG liability
No predicted genotoxic or mutagenic alerts No hepatotoxicity-associated moieties No cytotoxicity-prone structures No redox-cycling compounds |
No aggregators or colloidal formers
Non-chelating agents No Michael acceptors No predicted chemical instability No carcinogenicity-associated structures
|
Predicted ADME Profile: Designed to favor optimal biopharmaceutical properties
Highlights: diversity to explore SAR from day one, with feasible synthesis paths (from available building blocks), reduced toxicology liabilities and favourable ADME profile based on predictions.
What you can do with this collection
- Explore structure–activity relationships (SAR): Access 24 well-defined molecular series, each offering diverse scaffolds to map activity trends from the start.
- Prioritize experimental testing: Select top-ranked candidates for enzymatic and cellular assays of MERTK, supported by predicted potency and clean ADMET profiles (in silico).
- Accelerate iterative design: Expand fragments and modify R-groups using provided synthetic routes, enabling rapid optimization cycles and data-driven hit evolution.
Availability
Collection available for collaboration or licensing (by molecular series or full set). Contact us through our contact page.
References
- Myers KV, Amend SR, Pienta KJ (2019). Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment. Published in Molecular Cancer
Read the article : https://pubmed.ncbi.nlm.nih.gov/31088471/
- Huelse JM, Fridlyand DM, Earp S, DeRyckere D, Graham DK (2020). MERTK in cancer therapy: Targeting the receptor tyrosine kinase in tumor cells and the immune system. Published in Pharmacology & Therapeutics.
Read the article : https://pubmed.ncbi.nlm.nih.gov/32417270/ - UniProt (Q12866 – MERTK). Protein entry with details on function, ligands, and biological pathways.
View on Uniprot : https://www.uniprot.org/uniprotkb/Q12866/entry