Novel Para‐Phenylenediamine‐Based Derivatives as Receptor Tyrosine Kinase‐like Orphan Receptor 1 (ROR1) Inhibitors: An In Vitro Preliminary Characterization
Gerardina Smaldone, Maria Rosaria Miranda, Francesca Di Matteo, Valeria Napolitano, Michela Aliberti, Simona Musella, Veronica Di Sarno, Gianluigi Lauro, Giuseppe Bifulco, Giacomo Pepe, Giovanna Aquino, Mario Felice Tecce, Isabel Maria Gomez‐Monterrey, Pietro Campiglia
TL;DR
This study introduces new para-phenylenediamine-based compounds that inhibit ROR1, a promising cancer target, showing strong anticancer potential in lab tests.
Contribution
The paper presents novel para-phenylenediamine derivatives as effective ROR1 inhibitors with demonstrated anticancer activity.
Findings
Compound 17 shows strong affinity for ROR1 and inhibits its protumoral activity in cancer cell lines.
Pharmacokinetic tests reveal good stability for derivative 17, supporting further development.
The study confirms the potential of para-phenylenediamine as a scaffold for ROR1 inhibitors.
Abstract
ROR1 kinase is an underexplored promising target for the development of novel anticancer drugs, being strongly expressed in several cancer cell lines, but poorly in non‐tumor cells. This property, together with the scarce number of molecules effective against ROR1, leads to the design and development of a research program aimed at the discovery of new chemical entities able to inhibit ROR1 thus interfering with its protumoral activity. Step‐by‐step in silico studies guide the design and synthesis of para‐phenylenediamine‐based compounds. Surface plasmon resonance and Cellular Thermal Shift Assay analyses, coordinated with cytotoxicity assays carried out on JeKo‐1 (mantle cell lymphoma) and SH‐SY5Y (neuroblastoma cell) cell lines, demonstrate the strong affinity and the anticancer potential of the derivative 17, respectively, further confirming its mechanism of action. Moreover,…
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Taxonomy
TopicsNuclear Receptors and Signaling