| Autor: |
Muammar Fawwaz, Kenji Mishiro, Bambang Purwono, Ryuichi Nishii, Kazuma Ogawa |
| Jazyk: |
English<br />Spanish; Castilian |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Journal of Pharmacy & Pharmacognosy Research, Vol 12, Iss 2, Pp 231-242 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
0719-4250 |
| DOI: |
10.56499/jppres23.1743_12.2.231 |
| Popis: |
Context: Imaging the mutation status of non-small cell lung cancer (NSCLC) using radiolabeled tyrosine kinase inhibitor (TKI) analogs has garnered interest due to their unique interactions with the target epidermal growth factor receptor (EGFR). Rociletinib is a third-generation TKI that selectively inhibits the activated EGFR L858R/T790M mutations while sparing the wild-type EGFR. Aims: To synthesize a rociletinib analog for radioiodination purposes and evaluate its affinity for EGFR L858R/T790M using molecular docking and in vitro cytotoxicity assay. Methods: The rociletinib analog, N-{3-[(4-{[4-(4-acetylpiperazin-1-yl)-2-methoxyphenyl]amino}-5-(trifluoromethyl)pyrimidine-2-yl)amino] -5-iodophenyl} acrylamide (I-RMFZ), was produced by adding iodine into the diaminophenyl group and changing the position of the trifluoromethyl group. A simulation of molecular docking was conducted using the AutoDock Vina software suite. IC50 of I-RMFZ was determined using a cell cytotoxicity assay. Results: I-RMFZ was successfully synthesized through multistep reactions. Molecular docking revealed that I-RMFZ interacts with the EGFR L858R/T790M mutation. Cytotoxicity assay demonstrated that I-RMFZ had a high selectivity towards EGFR L858R/T779M mutation. Conclusions: I-RMFZ is notable for radioiodination and is anticipated to be comparable with in vivo features of rociletinib. Thus, I-RMFZ can potentially be developed as an imaging agent for NSCLC through preclinical assay. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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