Journal: Journal of Translational Medicine

Article Title: HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non–small cell lung cancer

doi: 10.1186/s12967-025-06613-0

Figure Lengend Snippet: The inhibitory activity of HS-10375 against EGFR C797S in vitro. A The chemical structure of HS-10375 and its interaction model binding to EGFR L858R/T790M/C797S. B , C The kinase inhibitory activity of HS-10375 against EGFR WT and EGFR C797S (Del19/T790M/C797S, L858R/T790M/C797S, Del19/C797S, and L858R/C797S), as well as other EGFR mutations (Del19, T790M, L858R, L858R/T790M, and Del19/T790M). D Mean IC 50 values for HS-10375 and TQB3804 in different EGFR mutations. All values are the average of two or three independent biological replicates. E The anti-proliferation activity of HS-10375 in A431 and Ba/F3 Del19/T790M/C797S cells. F The inhibitory activity of HS-10375 against other tyrosine kinases

Article Snippet: The primary antibodies p-EGFR (Tyr1068; #3777S), EGFR (#4267S), and p-ERK1/2 (#4370S) were obtained from Cell Signaling Technology, and GAPDH (#MA5-15738-A488) was purchased from Thermo Fisher.

Techniques: Activity Assay, In Vitro, Binding Assay

Journal: Journal of Translational Medicine

Article Title: HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non–small cell lung cancer

doi: 10.1186/s12967-025-06613-0

Figure Lengend Snippet: The inhibitory activity of HS-10375 against EGFR C797S in vitro. A The chemical structure of HS-10375 and its interaction model binding to EGFR L858R/T790M/C797S. B , C The kinase inhibitory activity of HS-10375 against EGFR WT and EGFR C797S (Del19/T790M/C797S, L858R/T790M/C797S, Del19/C797S, and L858R/C797S), as well as other EGFR mutations (Del19, T790M, L858R, L858R/T790M, and Del19/T790M). D Mean IC 50 values for HS-10375 and TQB3804 in different EGFR mutations. All values are the average of two or three independent biological replicates. E The anti-proliferation activity of HS-10375 in A431 and Ba/F3 Del19/T790M/C797S cells. F The inhibitory activity of HS-10375 against other tyrosine kinases

Article Snippet: The primary antibodies p-EGFR (Tyr1068; #3777S), EGFR (#4267S), and p-ERK1/2 (#4370S) were obtained from Cell Signaling Technology, and GAPDH (#MA5-15738-A488) was purchased from Thermo Fisher.

Techniques: Activity Assay, In Vitro, Binding Assay

Journal: Journal of Translational Medicine

Article Title: HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non–small cell lung cancer

doi: 10.1186/s12967-025-06613-0

Figure Lengend Snippet: The effects of HS-10375 on EGFR phosphorylation in vitro. A The cellular p-EGFR inhibition activity of HS-10375 and other EGFR TKIs. B – G Representative western blots comparing inhibition of EGFR-mediated signaling in Ba/F3 cells with different EGFR mutants by erlotinib, afatinib, osimertinib, and HS-10375. OR: osimertinib resistance. H Flow cytometry analysis of HS-10375 and osimertinib-induced apoptosis percentage in BaF3 EGFR -L858R/C797S, Ba/F3 EGFR -Del19/T790M/C797S, and PC9 EGFR -Del19/T790M/C797S cells

Article Snippet: The primary antibodies p-EGFR (Tyr1068; #3777S), EGFR (#4267S), and p-ERK1/2 (#4370S) were obtained from Cell Signaling Technology, and GAPDH (#MA5-15738-A488) was purchased from Thermo Fisher.

Techniques: Phospho-proteomics, In Vitro, Inhibition, Activity Assay, Western Blot, Flow Cytometry

Journal: Journal of Translational Medicine

Article Title: HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non–small cell lung cancer

doi: 10.1186/s12967-025-06613-0

Figure Lengend Snippet: The antitumor activity of HS-10375 against EGFR-mutant models in vivo. A Antitumor activity of HS-10375 and TQB3804 in PC9 EGFR-Del19/T790M/C797S xenograft model. B , C Antitumor activity of HS-10375 in Ba/F3 EGFR-Del19/T790M/C797S and Ba/F3 EGFR-L858R/T790M/C797S xenograft models. D Antitumor activity of HS-10375 in the PDX model LD1–0025–200717 (EGFR Del19/T790M/C797S). Tumor volume at the endpoint versus vehicle control was performed by two-way ANOVA (**, P < 0.01; ***, P < 0.001). E Plasma, tumor and brain concentration profiles of HS-10375 in the Ba/F3 EGFR-Del19/T790M/C797S xenograft model after single oral administration. F PK parameters of HS-10375 in the Ba/F3 EGFR-Del19/T790M/C797S xenograft model. G Western blot analysis of p-EGFR, p-ERK, and total ERK in the Ba/F3 EGFR-Del19/T790M/C797S xenograft tumors in mice that were dosed with 20 mg/kg of HS-10375

Article Snippet: The primary antibodies p-EGFR (Tyr1068; #3777S), EGFR (#4267S), and p-ERK1/2 (#4370S) were obtained from Cell Signaling Technology, and GAPDH (#MA5-15738-A488) was purchased from Thermo Fisher.

Techniques: Activity Assay, Mutagenesis, In Vivo, Control, Clinical Proteomics, Concentration Assay, Western Blot