gnf 5837  (MedChemExpress)

Journal: Acta Neuropathologica Communications

Article Title: TrkA activation sustains chemotherapy resistance in chemotolerant medulloblastoma cells

doi: 10.1186/s40478-026-02265-3

Figure Lengend Snippet: Trk inhibition sensitizes resistant MB cells to chemotherapy. A Representative WB analysis of MB-R cells displaying the activation status of TrkA in response to GNF-5837 or GW-441,756 treatments (48 h) at the indicated compound concentrations. B Bar graphs summarizing the % of Ki67 + cells in MB-R cells after 24 h of treatment with the indicated concentrations of GNF-5837 and GW-441,756. C Dose-response curves displaying the viability of MB-R cells when treated for 72 h with scalar doses of VECC, GNF-5837, GW-441,756, or the VECC + GNF-5837 and VECC + GW-441,756 combinations (1:10 fixed ratio). D Graph summarizing the synergistic action (Combination Index ≤ 1) of the VECC + GNF-5837 and VECC + GW-441,756 combinations in MB-R cells. E Bar graphs displaying the viability of MB-R cells after 48 h from treatment with VECC, GNF-5837, GW-441,756, or the VECC combinations with them as measured by Annexin-V staining. In HD-MB03-R cells: VECC 1U, GNF-5837 10µM, and GW-441,756 10µM; in HuTuP33-R cells: VECC 0.5U + GNF-5837 5µM, and VECC 1U + GW-441,756 10µM. F Bar graph displaying the viability of HD-MB03-R spheroids after 120 h from treatment with the indicated concentrations of VECC, GW-441,756, or their combination (1:10 ratio) by a resazurin assay. G , H Representative brightfield images ( G ) and relative volume estimation ( H ) of HD-MB03-R spheroids after 120 h from treatment with VECC (1U), GW-441,756 (10µM), or their combination. Original magnification 4X; scale bar, 200 μm. In all bar graphs, statistical analyses by one-way Anova with Tukey’s multiple comparisons test; * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: In dose-response experiments, MB cells were seeded in 96-well plates and, after 24 h, treated in triplicate with scalar doses of VECC, the TRK inhibitors GNF-5837 and GW-441,756, and the pan-Akt inhibitor GSK-690,693 (all from MedChemExpress, Monmouth Junction, NJ), or their combinations (at a fixed 1:10 ratio, respectively).

Techniques: Inhibition, Activation Assay, Staining, Resazurin Assay

Journal: Acta Neuropathologica Communications

Article Title: TrkA activation sustains chemotherapy resistance in chemotolerant medulloblastoma cells

doi: 10.1186/s40478-026-02265-3

Figure Lengend Snippet: Trk inhibition sensitizes resistant MB cells to chemotherapy. A Representative WB analysis of MB-R cells displaying the activation status of TrkA in response to GNF-5837 or GW-441,756 treatments (48 h) at the indicated compound concentrations. B Bar graphs summarizing the % of Ki67 + cells in MB-R cells after 24 h of treatment with the indicated concentrations of GNF-5837 and GW-441,756. C Dose-response curves displaying the viability of MB-R cells when treated for 72 h with scalar doses of VECC, GNF-5837, GW-441,756, or the VECC + GNF-5837 and VECC + GW-441,756 combinations (1:10 fixed ratio). D Graph summarizing the synergistic action (Combination Index ≤ 1) of the VECC + GNF-5837 and VECC + GW-441,756 combinations in MB-R cells. E Bar graphs displaying the viability of MB-R cells after 48 h from treatment with VECC, GNF-5837, GW-441,756, or the VECC combinations with them as measured by Annexin-V staining. In HD-MB03-R cells: VECC 1U, GNF-5837 10µM, and GW-441,756 10µM; in HuTuP33-R cells: VECC 0.5U + GNF-5837 5µM, and VECC 1U + GW-441,756 10µM. F Bar graph displaying the viability of HD-MB03-R spheroids after 120 h from treatment with the indicated concentrations of VECC, GW-441,756, or their combination (1:10 ratio) by a resazurin assay. G , H Representative brightfield images ( G ) and relative volume estimation ( H ) of HD-MB03-R spheroids after 120 h from treatment with VECC (1U), GW-441,756 (10µM), or their combination. Original magnification 4X; scale bar, 200 μm. In all bar graphs, statistical analyses by one-way Anova with Tukey’s multiple comparisons test; * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: In dose-response experiments, MB cells were seeded in 96-well plates and, after 24 h, treated in triplicate with scalar doses of VECC, the TRK inhibitors GNF-5837 and GW-441,756, and the pan-Akt inhibitor GSK-690,693 (all from MedChemExpress, Monmouth Junction, NJ), or their combinations (at a fixed 1:10 ratio, respectively).

Techniques: Inhibition, Activation Assay, Staining, Resazurin Assay

Journal: Journal of Neurochemistry

Article Title: Cerebral Dopamine Neurotrophic Factor ( CDNF ) Acts as a Trophic Factor Promoting Neuritogenesis in the Dorsal Root Ganglia ( DRG ) Neurons Through Activation of the PI3K Signaling Pathway

doi: 10.1111/jnc.70194

Figure Lengend Snippet: CDNF's trophic activity appears to be independent of both NGF and TrkA receptor signaling. Pharmacological inhibitor (GNF‐5837) of Tropomyosin Receptors kinase (+Trki) or anti‐nerve growth factor (NGF) antibody (+α‐NGF) or both (Trki+α‐NGF) were added to dorsal root ganglia (DRG) explants stimulated with NGF 30 ng/mL or cerebral dopamine neurotrophic factor (CDNF, 18 μg/mL). (A) Representative images of DRG explants immunostained with anti‐TuJ‐1 antibody (green) treated with NGF for 72 h (upper images) or with CDNF (lower images) in the absence (control—Ctr) or in the presence of Trki (+Trki—20 μM), anti‐NGF (+α‐NGF—10 μM) or both (Trki + α‐NGF). (B) Neurite length and (C) neuritic area for the conditions displayed in panel A. (D) Cell toxicity assays measured by LDH for the conditions displayed in panel A. Number of Intersections in the presence of NGF (E) or CDNF (F) for the conditions displayed in panel A. Area under the curve (AUC) relative to number of intersections in shown in the inset. The percentage of neurite outgrowth inhibition for each condition is shown at the top in (B). Scale bar = 300 μm. Data are presented as mean ± SEM from n = 3 independent experiments. One‐way ANOVA, with Tukey's post hoc test for significance. * p < 0.05 indicates statistical significance.

Article Snippet: Culture media were then replaced by medium only (deprived group), or media containing NGF (30 ng/mL or as stated in Figure legends), CDNF, or CDNF‐ΔKTEL (both at 1.8 μg/mL or 18 μg/mL or stated in Figure legends) for an additional 48 h. To unravel the signaling pathways involved in neuritogenesis, we incubated DRG cultures with wortmannin (400 nM ; Cat. No. W3144 Merck) or LY294002 (From 4 to 400 nM ); cat. No. S1105 Selleckchem, both are PI3K pathway inhibitors; rapamycin (20 nM ; Cat. No. S‐015 Merck), a mTOR pathway inhibitor; GNF ‐5837 (20 μM ; Cat. No. S7519 Selleckchem), a pan‐Trk inhibitor; and anti‐ NGF antibody (10 μM ; Cat. No. AF256 ‐ NA RD Systems, RRID:AB_2106738) to inhibit NGF binding to its receptor.

Techniques: Activity Assay, Control, Inhibition