TAS2940 fumarate is a brain-penetrating, orally active, irreversible, and selective pan-ERBB inhibitor. It exhibits IC50 values of 5.6 nM, 2.1 nM, and 1.0 nM against wild-type HER2, HER2 V777L, and A775_G776insYVMA, respectively. TAS2940 fumarate is utilized for researching tumors characterized by abnormalities in HER2 and EGFR.

TAS2940 fumarate, at concentrations ranging from 10-100 nM applied over a period of 3-48 hours, significantly elevates the protein levels of B-cell lymphoma 2 interacting mediator of cell death (BIM) and cleaved PARP. Furthermore, TAS2940 fumarate inhibits the phosphorylation of HER2, HER3, and their downstream proteins AKT and ERK. Additionally, TAS2940 fumarate demonstrates inhibitory activity against various cell lines including MCF10A_HER2, MCF10A_HER2/S310F, MCF10A_HER2/L755S, MCF10A_HER2/V777L, MCF10A_HER2/V842I, MCF10A_HER2/insYVMA, MCF10A_EGFR, MCF10A_EGFR (EGF+), MCF10A_EGFR/V769_D770insASV, and MCF10A_EGFR/D770_N771insSVD, with IC50 values of 2.27 nM, 1.98 nM, 3.74 nM, 1.54 nM, 3.28 nM, 1.91 nM, 9.38 nM, 0.804 nM, 5.64 nM, and 2.98 nM respectively.

TAS2940 fumarate administered orally at doses ranging from 3.1 to 25 mg/kg once daily for 14 days demonstrated effectiveness in inhibiting tumor growth within xenograft mouse models harboring ERBB abnormalities, such as HER2 amplification, HER2/EGFR exon 20 insertions, and EGFR vIII mutations. Pharmacokinetic parameters were also assessed, showing varied absorption and elimination profiles depending on the frequency of administration. For instance, following a single dose of 6.25 mg/kg, the peak concentration (Cmax) was 601±111 ng/mL and the area under the curve (AUC last) was 795±229 ng•h/mL. Repeated doses over seven days altered these figures significantly. The study utilized 6-week-old male BALB/cAJcl-nu/nu mice injected with different cancer cell lines including NCI-N87, MCF10A_HER2/insYVMA_v, and NCI-H1975 EGFR D770_N771insSVD to assess the compound's efficacy and pharmacokinetics.