Skip to main content

Table 2 ATP-competitive EGFR inhibitors

From: Emerging strategies to overcome resistance to third-generation EGFR inhibitors

Compound (reference) Structure Enzymatic activity Biological activity DMPK profile
13, JND3229 [102] EGFRL858R/T790M/C797S
IC50 = 5.8 nmol/L
BaF3-EGFRL858R/T790M/C797S
IC50 = 510 nmol/L
BaF3-EGFRDel19/T790M/C797S
IC50 = 320 nmol/L
N/A*
14 [103] EGFRWT
IC50 = 16 nmol/L
EGFRL858R/T790M/C797S
IC50 = 88 nmol/L
A431
GI50 = 3600 nmol/L
H1975
GI50 = 140 nmol/L
N/A
15 [104] EGFRL858R/T790M/C797S IC50 = 8 nmol/L A431
EC50 = 4000 nmol/L
H1975
EC50 = 400 nmol/L
N/A
16 [105, 106] EGFRL858R/T790M/C797S
IC50 = 630 nmol/L
H1975
IC50 = 1200 nmol/L
Liver microsomes (Human):
t1/2 (min) = 66.6, CLint (mL/min/kg) = 20.8
17 [107] EGFRWT
IC50 > 1000 nmol/L
EGFRL858R/T790M/C797S
IC50 = 27.5 nmol/L
BaF3-EGFRL858R/T790M/C797S
IC50 = 662 nmol/L
T1/2 (rat, minutes) = 8.36,
CLint (mL/min/kg) = 297.12
18 [108] EGFRL858R/T790M/C797S
IC50 = 7.2 nmol/L
HCC827
IC50 = 44 nmol/L
H1975
IC50 = 400 nmol/L
N/A
19 [109, 110] EGFRL858R/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] EGFRL858R/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):
AUCfree (h∙ng/mL) = 8.6
t1/2 (h) = 1.2
Cmax,free (μmol/L) = 0.012
21 [112] EGFRL858R/T790M/C797S
IC50 = 3.1 nmol/L
H1975
IC50 = 0.12 ± 0.09 μmol/L
BaF3-EGFRL858R/T790M/C797S
IC50 = 0.29 μmol/L
BaF3-EGFR19D/T790M/C797S IC50 = 0.31 μmol/L
N/A
22 [113] EGFRWT
IC50 > 1000 nmol/L
EGFRL858R/T790M/C797S
IC50 = 218.3 nmol/L
EGFRDel19/T790M/C797S
IC50 = 15.3 nmol/L
H1975
IC50 = 16,180 nmol/L
A431
IC50 = 20,480 nmol/L
BaF3-EGFRDel19/T790M/C797S
IC50 = 8510 nmol/L
N/A
23 [114] EGFRWT
IC50 = 430 nmol/L
EGFRDel19/T790M/C797S
IC50 = 0.2 nmol/L
BaF3-EGFRWT
IC50 = 1000 nmol/L
BaF3-EGFRDel19
IC50 = 180 nmol/L
BaF3-EGFRDel19/T790M
IC50 = 99 nmol/L
BaF3-EGFRDel19/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-EGFRL858R/T790M/C797S IC50 = 595.7 nmol/L
PC-9-EGFRDel19/T790M/C797S IC50 = 739.9 nmol/L
A549 IC50 = 2861.7 nmol/L
BaF3-EGFRWT IC50 = 519.82 nmol/L
BaF3-EGFRL858R/T790M/C797S IC50 = 0.16 nmol/L
BaF3-EGFRDel19/T790M/C797S IC50 = 0.23 nmol/L
N/A
26 [117] N/A BaF3-EGFRWT IC50 = 540 nmol/L
BaF3-EGFRL858R/T790M/C797S IC50 = 48.2 nmol/L
BaF3-EGFRDel19/T790M/C797S IC50 = 12 nmol/L
N/A
27 [115] EGFRWT
IC50 = 7.92 nmol/L
EGFRL858R/T790M/C797S
IC50 = 0.218 nmol/L
EGFRDel19/T790M/C797S
IC50 = 0.16 nmol/L
Antiproliferative Activity:
A431
IC50 = 154 nmol/L
BaF3-EGFRDel19/T790M/C797S
IC50 = 22 nmol/L
In vivo PK (mice, per os, 15 mg/kg):
AUC0-last = 57,037 (nmol/L∙h)
t1/2 (h) = 10.0
Plasma (nmol/L), 2 h = 3553
Tumor (nmol/kg), 2 h = 16,667
28 [118] EGFRWT
IC50 = 3.8 nmol/L
EGFRL858R/T790M/C797S
IC50 = 38.1 nmol/L
BaF3-EGFRL858R/T790M/C797S
IC50 < 1000 nmol/L
N/A
29, UPR1444 [119] EGFRWT
IC50 = 30 ± 4.8 nmol/L
EGFRL858R/T790M/C797S
IC50 = 110 ± 33 nmol/L
N/A N/A
  1. *N/A not available