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. 2022 Jul 15;15:94. doi: 10.1186/s13045-022-01311-6

Table 2.

ATP-competitive EGFR inhibitors

Compound (reference) Structure Enzymatic activity Biological activity DMPK profile
13, JND3229 [102] graphic file with name 13045_2022_1311_Figg_HTML.gif

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] graphic file with name 13045_2022_1311_Figh_HTML.gif

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] graphic file with name 13045_2022_1311_Figi_HTML.gif EGFRL858R/T790M/C797S IC50 = 8 nmol/L

A431

EC50 = 4000 nmol/L

H1975

EC50 = 400 nmol/L

 N/A
16 [105, 106] graphic file with name 13045_2022_1311_Figj_HTML.gif

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] graphic file with name 13045_2022_1311_Figk_HTML.gif

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] graphic file with name 13045_2022_1311_Figl_HTML.gif

EGFRL858R/T790M/C797S

IC50 = 7.2 nmol/L

HCC827

IC50 = 44 nmol/L

H1975

IC50 = 400 nmol/L

 N/A
19 [109, 110] graphic file with name 13045_2022_1311_Figm_HTML.gif

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] graphic file with name 13045_2022_1311_Fign_HTML.gif

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] graphic file with name 13045_2022_1311_Figo_HTML.gif

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] graphic file with name 13045_2022_1311_Figp_HTML.gif

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] graphic file with name 13045_2022_1311_Figq_HTML.gif

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] graphic file with name 13045_2022_1311_Figr_HTML.gif N/A

Biochemical potency:

BaF3 cells IC50 < 100 nmol/L

Antiproliferative activity:

BaF3 cells IC50 < 100 nmol/L

 N/A
25 [116] graphic file with name 13045_2022_1311_Figs_HTML.gif 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] graphic file with name 13045_2022_1311_Figt_HTML.gif 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] graphic file with name 13045_2022_1311_Figu_HTML.gif

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] graphic file with name 13045_2022_1311_Figv_HTML.gif

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] graphic file with name 13045_2022_1311_Figw_HTML.gif

EGFRWT

IC50 = 30 ± 4.8 nmol/L

EGFRL858R/T790M/C797S

IC50 = 110 ± 33 nmol/L

 N/A N/A

*N/A not available