The Synthesis and Initial Evaluation of MerTK Targeted PET Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Radiochemistry
2.3. Evaluation of the LogP
2.4. PET Imaging Study on Mice
3. Materials and Methods
3.1. Chemistry
3.1.1. Synthesis of UNC5650
3.1.2. Synthesis of UNC6429
3.1.3. Synthesis of MerTK-1
3.1.4. Synthesis of MerTK-2
3.1.5. Synthesis of MerTK-3/MerTK-4
3.1.6. Synthesis of MerTK-5
3.1.7. Synthesis of Compound MerTK-6
3.1.8. Microcapillary Electrophoresis (MCE) Assays
3.2. Radiochemistry
3.3. Evaluation of LogP
3.4. Mouse Model
3.5. PET Imaging
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Compound | Structure | MerTK IC50 (nM) a | Axl IC50 (nM) a | Tyro3 IC50 (nM) a | Flt3 IC50 (nM) a |
---|---|---|---|---|---|
MerTK-1 | 4.2 | 370 | 65 | 850 | |
MerTK-2 | 61 | 1700 | 180 | >30,000 | |
MerTK-4 | 13 | 4100 | 180 | >30,000 | |
MerTK-5 | 15 | 1100 | 190 | 1000 | |
MerTK-6 | 37 | 2100 | 120 | 5500 |
Kinase | Peptide Substrate | Kinase (nM) | ATP (µM) |
---|---|---|---|
Mer | 5-FAM-EFPIYDFLPAKKK-CONH2 | 1.7 | 22.3 |
Axl | 5-FAM-KKKKEEIYFFF-CONH2 | 16 | 200 |
Tyro3 | 5-FAM-EFPIYDFLPAKKK-CONH2 | 5 | 40 |
Flt3 | 5-FAM-KKKKEEIYFFF-CONH2 | 0.3 | 275 |
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Wang, L.; Zhou, Y.; Wu, X.; Ma, X.; Li, B.; Ding, R.; Stashko, M.A.; Wu, Z.; Wang, X.; Li, Z. The Synthesis and Initial Evaluation of MerTK Targeted PET Agents. Molecules 2022, 27, 1460. https://doi.org/10.3390/molecules27051460
Wang L, Zhou Y, Wu X, Ma X, Li B, Ding R, Stashko MA, Wu Z, Wang X, Li Z. The Synthesis and Initial Evaluation of MerTK Targeted PET Agents. Molecules. 2022; 27(5):1460. https://doi.org/10.3390/molecules27051460
Chicago/Turabian StyleWang, Li, Yubai Zhou, Xuedan Wu, Xinrui Ma, Bing Li, Ransheng Ding, Michael A. Stashko, Zhanhong Wu, Xiaodong Wang, and Zibo Li. 2022. "The Synthesis and Initial Evaluation of MerTK Targeted PET Agents" Molecules 27, no. 5: 1460. https://doi.org/10.3390/molecules27051460