Neratinib (HKI-272): Selectivity & Specificity

Neratinib (HKI-272) is a potent inhibitor of HER2 kinase (5.6 nmol/L), EGFR kinase (92 nM), MST1 (37.7 nM), EGFR (81 ± 9 nM), MAP4K4 (33.48 nM), MST2 (87.81 nM), HER2 (2–3 nM), HER4 (19 nM), BT474 (6.7 nM), EFM-192A (46.7 nM), UACC-812 (<5 nM), MDA-MB-361 (7.36 ± 2.65 nM), HCC1419 (3.94 ± 0.5 nM), HCC1569 (<5 nM), HCC1954 (325 nM), JIMT-1 (141.5 ± 9.61 nM), MDA-MB-453 (267.23 ± 22.52 nM), SKBR3 (10.2 nM), SUM-190 (10 ± 0.0 nM), SUM-225 (10 ± 0.0 nM), UACC-732 (650 ± 370 nM), UACC-893 (<5 nM), MCF7 (>3000 nM), T47D (890 nM), HCC1937 (750 nM), SUM-229PE (14 nM), MDA-MB-231 (496 ± 98 nM), MDA-MB-468 (36 nM), MCF10A HER2 WT (<2480 ± 50 nM), MCF10A G309A (<2470 ± 50 nM), MCF10A V777L (<21040 ± 570 nM), MCF10A D769H (<2980 ± 950 nM), MCF10A V842I (<2650 ± 210 nM), MCF10A del.755–759 (2.1 ± 0.2 nM), MCF10A L755S (15.6 ± 6 nM), MCF10A K75E (32 ± 8 nM), MCF10A L768S (<21050 ± 480 nM), MCF10A V773L (<2960 ± 380 nM), MCF10A R647K (<2650 ± 370 nM), MCF10A I655V (<2520 ± 420 nM), MCF10A K676R (<2385 ± 270 nM), MCF10A Q680R (<2550 ± 190 nM), MEK1, MEK2, P-gp, EGFR Cys-797, EGFR T790M, HER2 P780_Y781insGSP, HER2 K753E, HER2 L755S, HER2 D769Y, PIK3CA, PD-1, membrane-bound ATP transporter. Neratinib (HKI-272) exhibits the greatest inhibitory potency toward HER2 (IC50 = 2–3 nM).