Extended Data Fig. 8: Characterization of oral candidate AM-9022.
a, Mitotic pH3 and pharmacokinetic (PK) analysis. OVCAR-3 cells were treated for 24 h with DMSO, AM-1882, or AM-9022 at indicated concentrations. Cells were stained to detect DNA and pH3. Graphs of compound concentration-response profiles presented as pH3 percentage and EC50 values (n = 2 independent experiments in duplicate). Mouse plasma PK area-under-the-curve (AUC) values (µM·h) were determined after a single oral (p.o.) dose of AM-1882 (100 mg per kg) or AM-9022 (10 mg per kg) (n = 3 mice per group). b, Human and mouse KIF18A motor MT-ATPase assays performed for AM-9022, as assessed by ADP-Glo. Graph of AM-9022 concentration-response profiles presented as MT-ATPase luminescence signal relative to percentage of DMSO control (POC) and IC50 values (n = 2 independent experiments). c, End of study mouse plasma PK profile from OVCAR-3 CDX tumor model. Mice were administered a p.o. dose of AM-9022 (30 mg per kg) for 18 d. Scatterplot shows the mouse PK profile presented as mean plasma concentration versus time (n = 2 mice per time point) and AUC values (µM·h). d, Mitotic pH3 imaging analysis. JIMT-1 cells were treated for 24 h with DMSO, AM-0277, AM-1882, AM-5308, or AM-9022 at the indicated concentrations. Cells were stained to detect DNA and pH3. Graphs of compound concentration-response profiles presented as pH3 percentage and EC50 values (n = 2 independent experiments in duplicate). e, End of study mouse plasma PK profile from JIMT-1 CDX tumor model. Mice were administered a p.o. dose of AM-9022 (30 or 100 mg per kg) for 21 d. Scatterplot shows the mouse PK profile presented as mean plasma concentration versus time (n = 2 mice per time point) and AUC values (µM·h).
