Journal: Experimental neurology

Article Title: Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides

doi: 10.1016/j.expneurol.2016.06.021

Figure Lengend Snippet: Effects of a neurokinin (NK)-1 receptor antagonist (RA), netupitant, on micturition reflex function from open outlet, continuous fill cystometry in NGF-OE mice and littermate WT mice at postnatal (P) day 7, P14, P28 and Adult (A). Intravesical netupitant (0.1 μg/ml) significantly (p ≤ 0.01) increased voided volume (A) and intercontraction interval (ICI) (B) in NGF-OE mice at all postnatal ages examined. Intravesical netupitant (0.1 μg/ml) was without effect on voided volume (A) or ICI (B) in WT mice except at P14 where there was a significant (p ≤ 0.01) increase in voided volume. *, p ≤ 0.01 compared to vehicle. Values are means ± S.E.M. (n = 6–8 for each group).

Article Snippet: The effectiveness of intravesical netupitant (Med Chem Express (MCE), Monmouth Junction, NJ; 0.1 μg/ml) administration was evaluated in littermate WT and NGF-OE mice from various postnatal ages (P7-A).

Techniques:

Journal: Experimental neurology

Article Title: Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides

doi: 10.1016/j.expneurol.2016.06.021

Figure Lengend Snippet: Effects of a neurokinin (NK)-1 receptor antagonist (RA), netupitant, on micturition reflex function from open outlet, continuous fill cystometry in NGF-OE mice and littermate WT mice at postnatal (P) day 7, P14, P28 and Adult (A). Intravesical netupitant (0.1 μg/ml) significantly (p ≤ 0.01) decreased the number of nonvoiding contractions (NVCs) in NGF-OE mice at P7 and P28 but was without effect on NVCs in WT mice that exhibited few NVCs (A). Intravesical netupitant (0.1 μg/ml) was without effect on bladder pressures (baseline (BP), threshold pressure (TP), peak micturition pressure (MP)) in NGF-OE and WT mice at any postnatal age examined (B). *, p ≤ 0.01 compared to vehicle. Values are means ± S.E.M. (n = 6–8 for each group).

Article Snippet: The effectiveness of intravesical netupitant (Med Chem Express (MCE), Monmouth Junction, NJ; 0.1 μg/ml) administration was evaluated in littermate WT and NGF-OE mice from various postnatal ages (P7-A).

Techniques:

Journal: OncoTargets and therapy

Article Title: Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting

doi: 10.2147/OTT.S158570

Figure Lengend Snippet: Formulations of approved NK 1 RAs

Article Snippet: Aprepitant (Emend; Merck, Whitehouse Station, NJ), rolapitant (Varubi; Tesaro, Waltham, MA), and netupitant (Akynzeo; Helsinn Therapeutics, Iselin, NJ) are orally administered.

Techniques: Capsules, Suspension

Journal: OncoTargets and therapy

Article Title: Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting

doi: 10.2147/OTT.S158570

Figure Lengend Snippet: Comparative pharmacokinetic parameters and NK 1 -receptor occupancy for approved NK 1 -receptor antagonists in healthy volunteers

Article Snippet: Aprepitant (Emend; Merck, Whitehouse Station, NJ), rolapitant (Varubi; Tesaro, Waltham, MA), and netupitant (Akynzeo; Helsinn Therapeutics, Iselin, NJ) are orally administered.

Techniques:

Journal: OncoTargets and therapy

Article Title: Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting

doi: 10.2147/OTT.S158570

Figure Lengend Snippet: CRs in three-drug vs two-drug regimen trials in HEC (approved agents at recommended doses)

Article Snippet: Aprepitant (Emend; Merck, Whitehouse Station, NJ), rolapitant (Varubi; Tesaro, Waltham, MA), and netupitant (Akynzeo; Helsinn Therapeutics, Iselin, NJ) are orally administered.

Techniques: Control

Journal: OncoTargets and therapy

Article Title: Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting

doi: 10.2147/OTT.S158570

Figure Lengend Snippet: Nausea control in three-drug vs two-drug regimen trials in HEC (approved agents at recommended doses)

Article Snippet: Aprepitant (Emend; Merck, Whitehouse Station, NJ), rolapitant (Varubi; Tesaro, Waltham, MA), and netupitant (Akynzeo; Helsinn Therapeutics, Iselin, NJ) are orally administered.

Techniques: Control

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

Journal: Journal of Pharmaceutical Analysis

Article Title: Simulation of the oxidative metabolization pattern of netupitant, an NK 1 receptor antagonist, by electrochemistry coupled to mass spectrometry

doi: 10.1016/j.jpha.2021.03.011

Figure Lengend Snippet: Three-dimensional mass voltammogram ( m / z 520–615) of netupitant ( m / z 579.2551) and its oxidation products in the potential range of 0–2500 mV vs. Pd/H 2 .

Article Snippet: Netupitant was purchased from Shanghai Seebio Biotech, Inc. (Shanghai, China).

Techniques:

Journal: Journal of Pharmaceutical Analysis

Article Title: Simulation of the oxidative metabolization pattern of netupitant, an NK 1 receptor antagonist, by electrochemistry coupled to mass spectrometry

doi: 10.1016/j.jpha.2021.03.011

Figure Lengend Snippet: Extracted ion chromatograms of the electrochemically generated oxidation species ( m / z 583.2140, m / z 539.2239, m / z 538.1924, m / z 553.2397, m / z 563.2245, m / z 496.1818, m / z 567.2189, m / z 565.2035, m / z 609.2292, and m / z 524.1769) of netupitant ( m / z 579.2551) at 1700 mV.

Article Snippet: Netupitant was purchased from Shanghai Seebio Biotech, Inc. (Shanghai, China).

Techniques: Generated

Journal: Journal of Pharmaceutical Analysis

Article Title: Simulation of the oxidative metabolization pattern of netupitant, an NK 1 receptor antagonist, by electrochemistry coupled to mass spectrometry

doi: 10.1016/j.jpha.2021.03.011

Figure Lengend Snippet: Proposed structures of the electrochemically generated metabolites of netupitant.

Article Snippet: Netupitant was purchased from Shanghai Seebio Biotech, Inc. (Shanghai, China).

Techniques: Generated

Journal: Journal of Pharmaceutical Analysis

Article Title: Simulation of the oxidative metabolization pattern of netupitant, an NK 1 receptor antagonist, by electrochemistry coupled to mass spectrometry

doi: 10.1016/j.jpha.2021.03.011

Figure Lengend Snippet: Relative signals of the most relevant protonated ions of the electrochemically generated products of netupitant versus the applied potential. Inset: zoomed-in view of the relative signals of the protonated species resulting from the further electrochemical reactions undergone by the N , N -demethylated compound that had gone through a previous oxidation reaction with a carbonyl group ( m / z 565.2035).

Article Snippet: Netupitant was purchased from Shanghai Seebio Biotech, Inc. (Shanghai, China).

Techniques: Generated

Journal: Journal of Pharmaceutical Analysis

Article Title: Simulation of the oxidative metabolization pattern of netupitant, an NK 1 receptor antagonist, by electrochemistry coupled to mass spectrometry

doi: 10.1016/j.jpha.2021.03.011

Figure Lengend Snippet: Comparison between the reported phase I biotransformation of netupitant in vivo [ 10 ] and its electrochemically mimicked oxidation.

Article Snippet: Netupitant was purchased from Shanghai Seebio Biotech, Inc. (Shanghai, China).

Techniques: Comparison, In Vivo

Journal: Journal of Pharmaceutical Analysis

Article Title: Simulation of the oxidative metabolization pattern of netupitant, an NK 1 receptor antagonist, by electrochemistry coupled to mass spectrometry

doi: 10.1016/j.jpha.2021.03.011

Figure Lengend Snippet: MS/MS fragmentation pattern of netupitant ( m / z 579.2551) at 28.5 min (compound A in Fig. 3 ).

Article Snippet: Netupitant was purchased from Shanghai Seebio Biotech, Inc. (Shanghai, China).

Techniques: Tandem Mass Spectroscopy