Figure 1.
Tolinapant target engagement and induction of cell death in in vitro TCL models. (A) cIAP1 (by level reduction) and XIAP (by XIAP:SMAC complex immunoprecipitation) antagonism in mouse BW5147 cells treated with tolinapant for 2 hours. (B) cIAP1/2 and XIAP antagonism in human HH cells treated with tolinapant for 2 hours. (C) Cell viability (CellTiter-Glo [CTG]) assay data after 72 hours’ treatment of 4 mouse TCL cell lines with tolinapant alone. (D) As for panel C, except treated with tolinapant plus 10 ng/mL mouse TNF-α. (E) Cell viability (CTG) assay data after 72 hours of treatment of 5 human TCL cell lines with tolinapant alone. (F) As for panel E, except treated with tolinapant plus 10 ng/mL human TNF-α. (G) Western blots of BW5147 cell lysates after 24-hour treatment with tolinapant or tolinapant plus 10 ng/mL TNF-α. (H) BW5147 viability after 24-hour treatment with tolinapant or tolinapant plus TNF-α by cytometry (propidium iodide [PI] and cleaved caspase-3 dual staining [CC3]).

Tolinapant target engagement and induction of cell death in in vitro TCL models. (A) cIAP1 (by level reduction) and XIAP (by XIAP:SMAC complex immunoprecipitation) antagonism in mouse BW5147 cells treated with tolinapant for 2 hours. (B) cIAP1/2 and XIAP antagonism in human HH cells treated with tolinapant for 2 hours. (C) Cell viability (CellTiter-Glo [CTG]) assay data after 72 hours’ treatment of 4 mouse TCL cell lines with tolinapant alone. (D) As for panel C, except treated with tolinapant plus 10 ng/mL mouse TNF-α. (E) Cell viability (CTG) assay data after 72 hours of treatment of 5 human TCL cell lines with tolinapant alone. (F) As for panel E, except treated with tolinapant plus 10 ng/mL human TNF-α. (G) Western blots of BW5147 cell lysates after 24-hour treatment with tolinapant or tolinapant plus 10 ng/mL TNF-α. (H) BW5147 viability after 24-hour treatment with tolinapant or tolinapant plus TNF-α by cytometry (propidium iodide [PI] and cleaved caspase-3 dual staining [CC3]).

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