netupitant  (MGI Pharma)

Journal: Cancers

Article Title: Netupitant Inhibits the Proliferation of Breast Cancer Cells by Targeting AGK

doi: 10.3390/cancers16223807

Figure Lengend Snippet: Netupitant demonstrates the potential to inhibit the proliferation of breast cancer cells. ( A ) Validation of gene silencing efficiency for three siRNA sequences. ( B ) Growth curve assay following AGK gene silencing. ( C ) Clonal formation assay subsequent to AGK gene silencing. ( D ) Identification of five candidate compounds targeting AGK through virtual screening. ( E ) Assessment of the inhibitory capacity of these five candidate compounds on breast cancer cell proliferation via CCK8 assay. ( F ) Root Mean Square Deviation (RMSD) analysis of AGK and Netupitant obtained from molecular dynamics simulation. ( G ) Binding site analysis showing where Netupitant interacts with AGK, including the relevant amino acids involved in this interaction. ( H ) BIL analysis conducted to evaluate the affinity between AGK protein and Netupitant. * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Molecular dynamics simulations and BLI assays confirmed the interaction between the compound Netupitant and AGK, while key amino acids involved in this interaction site were preliminarily identified, establishing a foundation for potential future drug development.

Techniques: Biomarker Discovery, Tube Formation Assay, CCK-8 Assay, Binding Assay

Journal: Cancers

Article Title: Netupitant Inhibits the Proliferation of Breast Cancer Cells by Targeting AGK

doi: 10.3390/cancers16223807

Figure Lengend Snippet: Netupitant inhibits proliferation of breast cancer cells in vitro by inducing apoptosis. ( A ) IC50 values of Netupitant on SK-BR-3 and MDA-MB-231 cell lines. ( B ) Clonal formation assay following treatment with Netupitant. ( C ) Annexin V/PI staining for apoptosis assessment after 48h treatment. ( D ) Upregulation of apoptosis-related proteins subsequent to Netupitant treatment. * p < 0.05; ** p < 0.01; *** p < 0.001; ns: no significant difference.

Article Snippet: Molecular dynamics simulations and BLI assays confirmed the interaction between the compound Netupitant and AGK, while key amino acids involved in this interaction site were preliminarily identified, establishing a foundation for potential future drug development.

Techniques: In Vitro, Tube Formation Assay, Staining

Journal: Cancers

Article Title: Netupitant Inhibits the Proliferation of Breast Cancer Cells by Targeting AGK

doi: 10.3390/cancers16223807

Figure Lengend Snippet: Netupitant inhibits PI3K/AKT/mTOR signaling pathway in vitro. ( A ) Expression levels of AGK protein following treatment with Netupitant. ( B ) Assessment of phosphorylation status of proteins associated with PI3K/AKT signaling pathway after Netupitant treatment. * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Molecular dynamics simulations and BLI assays confirmed the interaction between the compound Netupitant and AGK, while key amino acids involved in this interaction site were preliminarily identified, establishing a foundation for potential future drug development.

Techniques: In Vitro, Expressing, Phospho-proteomics

Journal: Cancers

Article Title: Netupitant Inhibits the Proliferation of Breast Cancer Cells by Targeting AGK

doi: 10.3390/cancers16223807

Figure Lengend Snippet: Netupitant inhibits proliferation of breast cancer cells in vivo. ( A ) Overview of in vivo experimental procedure. ( B ) Tumor volume growth curve. ( C ) Photograph of excised tumor specimens. ( D ) Relative tumor volume change curve. ( E ) Measurement of tumor weight. ( F ) Body weight progression curve. ( G ) HE and Ki-67 staining images of tumor tissues. * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: Molecular dynamics simulations and BLI assays confirmed the interaction between the compound Netupitant and AGK, while key amino acids involved in this interaction site were preliminarily identified, establishing a foundation for potential future drug development.

Techniques: In Vivo, Staining

Journal: Cancers

Article Title: Netupitant Inhibits the Proliferation of Breast Cancer Cells by Targeting AGK

doi: 10.3390/cancers16223807

Figure Lengend Snippet: Netupitant induces apoptosis in tumor cells in vivo through the PI3K/AKT/mTOR signaling pathway. ( A ) TUNEL staining images of tumor tissues. ( B ) The degree of phosphorylation of PI3K/AKT signaling pathway-related proteins in tumor tissues following Netupitant treatment. #1: mice1; #2: mice2; * p < 0.05; ** p < 0.01; *** p < 0.001. ( C ) Netupitant, by inhibiting AGK, decreases the phosphorylation of PTEN, and thereby reduces the phosphorylation activation of AKT and mTOR.

Article Snippet: Molecular dynamics simulations and BLI assays confirmed the interaction between the compound Netupitant and AGK, while key amino acids involved in this interaction site were preliminarily identified, establishing a foundation for potential future drug development.

Techniques: In Vivo, TUNEL Assay, Staining, Phospho-proteomics, Activation Assay