Novel Para‐Phenylenediamine‐Based Derivatives as Receptor Tyrosine Kinase‐like Orphan Receptor 1 (ROR1) Inhibitors: An In Vitro Preliminary Characterization
Copyright policy )Novel Para‐Phenylenediamine‐Based Derivatives as Receptor Tyrosine Kinase‐like Orphan Receptor 1 (ROR1) Inhibitors: An In Vitro Preliminary Characterization
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, pharmacokinetic assessment reveals a good stability profile for derivative 17, paving the way for additional SAR studies on the para‐phenylenediamine as a scaffold for developing new ROR1 inhibitors.
synthesis, Molecular Structure, Dose-Response Relationship, Drug, binding assays; cytotoxic effects; kinase inhibitors; novel chemotypes; synthesis, binding assays, Antineoplastic Agents, Phenylenediamines, Receptor Tyrosine Kinase-like Orphan Receptors, synthesis * novel chemotype * kinase inhibitors * binding assay * cytotoxic effect, Molecular Docking Simulation, cytotoxic effects, Structure-Activity Relationship, Cell Line, Tumor, novel chemotypes, kinase inhibitors, Humans, Drug Screening Assays, Antitumor, Protein Kinase Inhibitors, Research Article, Cell Proliferation
synthesis, Molecular Structure, Dose-Response Relationship, Drug, binding assays; cytotoxic effects; kinase inhibitors; novel chemotypes; synthesis, binding assays, Antineoplastic Agents, Phenylenediamines, Receptor Tyrosine Kinase-like Orphan Receptors, synthesis * novel chemotype * kinase inhibitors * binding assay * cytotoxic effect, Molecular Docking Simulation, cytotoxic effects, Structure-Activity Relationship, Cell Line, Tumor, novel chemotypes, kinase inhibitors, Humans, Drug Screening Assays, Antitumor, Protein Kinase Inhibitors, Research Article, Cell Proliferation
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