Table 2. Selectivity of pirtobrutinib in... | American Society of Hematology

Table 2.

Selectivity of pirtobrutinib in cell-based assays

Kinase	n	Pirtobrutinib IC₅₀, mean ± SD, nM	Fold selectivity vs BTK∗	Cell assay readout
BTK	3	0.66 ± 0.34	1	Competitive displacement of tracer
TEC	3	70.46 ± 20.30	106.8	Competitive displacement of tracer
BRK/PTK6	3	360.47 ± 198.56	546.2	Competitive displacement of tracer
TXK	3	>5000†	>7600	Competitive displacement of tracer
YES1	3	>5000†	>7600	Competitive displacement of tracer
CSK	3	>5000†	>7600	Competitive displacement of tracer
FYN	3	>5000†	>7600	Competitive displacement of tracer
ERBB4	2	>10 000†	N/D	Phosphorylation of C-terminal tail
MEK1/MEK2	3	12 600 ± 2400	N/D	Phosphorylation of ERK1/2 (HCT116 cells)
MEK1/MEK2	3	3790 ± 1310	N/D	Phosphorylation of ERK1/2 (A375 cells)

Kinase	n	Pirtobrutinib IC₅₀, mean ± SD, nM	Fold selectivity vs BTK∗	Cell assay readout
BTK	3	0.66 ± 0.34	1	Competitive displacement of tracer
TEC	3	70.46 ± 20.30	106.8	Competitive displacement of tracer
BRK/PTK6	3	360.47 ± 198.56	546.2	Competitive displacement of tracer
TXK	3	>5000†	>7600	Competitive displacement of tracer
YES1	3	>5000†	>7600	Competitive displacement of tracer
CSK	3	>5000†	>7600	Competitive displacement of tracer
FYN	3	>5000†	>7600	Competitive displacement of tracer
ERBB4	2	>10 000†	N/D	Phosphorylation of C-terminal tail
MEK1/MEK2	3	12 600 ± 2400	N/D	Phosphorylation of ERK1/2 (HCT116 cells)
MEK1/MEK2	3	3790 ± 1310	N/D	Phosphorylation of ERK1/2 (A375 cells)

N/D, not determined; n, number of samples; SD, standard deviation.

Fold selectivity values vs BTK were calculated for those kinases assayed in the NanoBRET competitive displacement assay.

When data values did not fit an IC₅₀ curve, the top dose tested was used for estimating mean.