Table 2 ATP-competitive EGFR inhibitors

13, JND3229 [102]

EGFR^{L858R/T790M/C797S}

IC₅₀ = 5.8 nmol/L

BaF3-EGFR^{L858R/T790M/C797S}

IC₅₀ = 510 nmol/L

BaF3-EGFR^{Del19/T790M/C797S}

IC₅₀ = 320 nmol/L

N/A*

14 [103]

EGFR^WT

IC₅₀ = 16 nmol/L

EGFR^{L858R/T790M/C797S}

IC₅₀ = 88 nmol/L

A431

GI₅₀ = 3600 nmol/L

H1975

GI₅₀ = 140 nmol/L

N/A

15 [104]

EGFR^{L858R/T790M/C797S} IC₅₀ = 8 nmol/L

A431

EC₅₀ = 4000 nmol/L

H1975

EC₅₀ = 400 nmol/L

N/A

16 [105, 106]

EGFR^{L858R/T790M/C797S}

IC₅₀ = 630 nmol/L

H1975

IC₅₀ = 1200 nmol/L

Liver microsomes (Human):

t_1/2 (min) = 66.6, CLint (mL/min/kg) = 20.8

17 [107]

EGFR^WT

IC₅₀ > 1000 nmol/L

EGFR^{L858R/T790M/C797S}

IC₅₀ = 27.5 nmol/L

BaF3-EGFR^{L858R/T790M/C797S}

IC₅₀ = 662 nmol/L

T_1/2 (rat, minutes) = 8.36,

CLint (mL/min/kg) = 297.12

18 [108]

EGFR^{L858R/T790M/C797S}

IC₅₀ = 7.2 nmol/L

HCC827

IC₅₀ = 44 nmol/L

H1975

IC₅₀ = 400 nmol/L

N/A

19 [109, 110]

EGFR^{L858R/T790M/C797S}

IC₅₀ = 18 nmol/L

HCC827

IC₅₀ = 0.88 nmol/L

H1975

IC₅₀ = 200 nmol/L

A549

IC₅₀ = 2910 nmol/L

A431

IC₅₀ > 10,000 nmol/L

N/A

20 [111]

EGFR^{L858R/T790M/C797S}

IC₅₀ = 8.5 nmol/L

EGFR CTG

EC₅₀:

HCC827

IC₅₀ < 14 nmol/L

H1975

IC₅₀ = 51 ± 19 nmol/L

A431

IC₅₀ = 1675 ± 402 nmol/L

A549

IC₅₀ = 3700 nmol/L

H358

IC₅₀ = 3700 nmol/L

In vivo PK (mice, IP, 20 mg/kg):

AUC_free (h∙ng/mL) = 8.6

t_1/2 (h) = 1.2

C_max,free (μmol/L) = 0.012

21 [112]

EGFR^{L858R/T790M/C797S}

IC₅₀ = 3.1 nmol/L

H1975

IC₅₀ = 0.12 ± 0.09 μmol/L

BaF3-EGFR^{L858R/T790M/C797S}

IC₅₀ = 0.29 μmol/L

BaF3-EGFR^{19D/T790M/C797S} IC₅₀ = 0.31 μmol/L

N/A

22 [113]

EGFR^WT

IC₅₀ > 1000 nmol/L

EGFR^{L858R/T790M/C797S}

IC₅₀ = 218.3 nmol/L

EGFR^{Del19/T790M/C797S}

IC₅₀ = 15.3 nmol/L

H1975

IC₅₀ = 16,180 nmol/L

A431

IC₅₀ = 20,480 nmol/L

BaF3-EGFR^{Del19/T790M/C797S}

IC₅₀ = 8510 nmol/L

N/A

23 [114]

EGFR^WT

IC₅₀ = 430 nmol/L

EGFR^{Del19/T790M/C797S}

IC₅₀ = 0.2 nmol/L

BaF3-EGFR^WT

IC₅₀ = 1000 nmol/L

BaF3-EGFR^Del19

IC₅₀ = 180 nmol/L

BaF3-EGFR^Del19/T790M

IC₅₀ = 99 nmol/L

BaF3-EGFR^{Del19/T790M/C797S}

IC₅₀ = 63 nmol/L

N/A

24 [115]

N/A

Biochemical potency:

BaF3 cells IC₅₀ < 100 nmol/L

Antiproliferative activity:

BaF3 cells IC₅₀ < 100 nmol/L

N/A

25 [116]

N/A

Antiproliferative activity:

PC-9-EGFR^{L858R/T790M/C797S} IC₅₀ = 595.7 nmol/L

PC-9-EGFR^{Del19/T790M/C797S} IC₅₀ = 739.9 nmol/L

A549 IC₅₀ = 2861.7 nmol/L

BaF3-EGFR^WT IC₅₀ = 519.82 nmol/L

BaF3-EGFR^{L858R/T790M/C797S} IC₅₀ = 0.16 nmol/L

BaF3-EGFR^{Del19/T790M/C797S} IC₅₀ = 0.23 nmol/L

N/A

26 [117]

N/A

BaF3-EGFR^WT IC₅₀ = 540 nmol/L

BaF3-EGFR^{L858R/T790M/C797S} IC₅₀ = 48.2 nmol/L

BaF3-EGFR^{Del19/T790M/C797S} IC₅₀ = 12 nmol/L

N/A

27 [115]

EGFR^WT

IC₅₀ = 7.92 nmol/L

EGFR^{L858R/T790M/C797S}

IC₅₀ = 0.218 nmol/L

EGFR^{Del19/T790M/C797S}

IC₅₀ = 0.16 nmol/L

Antiproliferative Activity:

A431

IC₅₀ = 154 nmol/L

BaF3-EGFR^{Del19/T790M/C797S}

IC₅₀ = 22 nmol/L

In vivo PK (mice, per os, 15 mg/kg):

AUC_0-last = 57,037 (nmol/L∙h)

t_1/2 (h) = 10.0

Plasma (nmol/L), 2 h = 3553

Tumor (nmol/kg), 2 h = 16,667

28 [118]

EGFR^WT

IC₅₀ = 3.8 nmol/L

EGFR^{L858R/T790M/C797S}

IC₅₀ = 38.1 nmol/L

BaF3-EGFR^{L858R/T790M/C797S}

IC₅₀ < 1000 nmol/L

N/A

29, UPR1444 [119]

EGFR^WT

IC₅₀ = 30 ± 4.8 nmol/L

EGFR^{L858R/T790M/C797S}

IC₅₀ = 110 ± 33 nmol/L

N/A

N/A