canertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.7
|
pKd |
22 |
|
⤷ |
pKd
9.7
(Kd 1.9x10-10 M)
[22]
|
afatinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.6
|
pKd |
22 |
|
⤷ |
pKd
9.6
(Kd 2.5x10-10 M)
[22]
|
erlotinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.2
|
pKd |
22 |
|
⤷ |
pKd
9.2
(Kd 6.7x10-10 M)
[22]
|
gefitinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.0 – 9.0
|
pKd |
19,22 |
|
⤷ |
pKd
9.0
(Kd 1x10-9 M)
[22]
pKd
9.0
(Kd 1.1x10-9 M)
[19]
|
MS154
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.7
|
pKd |
19 |
|
⤷ |
pKd
8.7
(Kd 1.8x10-9 M)
[19]
Description: Dissociation constant determined for wild type EGFR in a competitive binding assay.
|
MS39
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.0
|
pKd |
19 |
|
⤷ |
pKd
8.0
(Kd 1.1x10-8 M)
[19]
Description: Dissociation constant determined for wild type EGFR in a competitive binding assay.
|
WZ4002
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.3
|
pKd |
101 |
|
⤷ |
pKd
7.3
(Kd 4.6x10-8 M)
[101]
|
xiliertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
10.3
|
pKi |
72 |
|
⤷ |
pKi
10.3
(Ki 5x10-11 M)
[72]
|
gefitinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.3
|
pKi |
90 |
|
⤷ |
pKi
8.3
(Ki 5.5x10-9 M)
[90]
|
PD166285
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.1
|
pKi |
64 |
|
⤷ |
pKi
7.1
(Ki 8.75x10-8 M)
[64]
|
rociletinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.5
|
pKi |
86 |
|
⤷ |
pKi
6.5
(Ki 3.033x10-7 M)
[86]
|
AG 9
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
<3.4
|
pKi |
31 |
|
⤷ |
pKi
<3.4
(Ki >4x10-4 M)
[31]
Description: Measuring phosphorylation of the EGFR exogenous substrate polyGAT [poly(Glu6Ala3Tyr)]
|
compound 56 [PMID: 8568816]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
11.2
|
pIC50 |
10 |
|
⤷ |
pIC50
11.2
(IC50 6x10-12 M)
[10]
|
BPIQ-I
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
10.6
|
pIC50 |
74 |
|
⤷ |
pIC50
10.6
(IC50 2.5x10-11 M)
[74]
|
EGFR/ErbB-2/ErbB-4 inhibitor
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.5
|
pIC50 |
47 |
|
⤷ |
pIC50
9.5
(IC50 3x10-10 M)
[47]
|
tesevatinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.5
|
pIC50 |
32 |
|
⤷ |
pIC50
9.5
(IC50 3x10-10 M)
[32]
|
mifanertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.4
|
pIC50 |
96 |
|
⤷ |
pIC50
9.4
(IC50 4x10-10 M)
[96]
|
PD 174265
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.4
|
pIC50 |
27 |
|
⤷ |
pIC50
9.4
(IC50 4.5x10-10 M)
[27]
|
allitinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.3
|
pIC50 |
94 |
|
⤷ |
pIC50
9.3
(IC50 5x10-10 M)
[94]
|
erlotinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.0
|
pIC50 |
100 |
|
⤷ |
pIC50
9.0
(IC50 1x10-9 M)
[100]
|
nazartinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
>9.0
|
pIC50 |
57 |
|
⤷ |
pIC50
>9.0
(IC50 <1x10-9 M)
[57]
Description: Biochemical assay using EGFR L858R/T790M with a 90 minute preincubation with the inhibitor.
|
pirotinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
9.0
|
pIC50 |
40 |
|
⤷ |
pIC50
9.0
(IC50 1x10-9 M)
[40]
|
zorifertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.1 – 9.5
|
pIC50 |
98 |
|
⤷ |
pIC50
9.5
(IC50 3x10-10 M)
[98]
Description: Inhibition of wild type EGFR in vitro, at Km of ATP.
pIC50
8.1
(IC50 7.2x10-9 M)
[98]
Description: Inhibition of EGFRL858R in vitro.
|
canertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.8
|
pIC50 |
77 |
|
⤷ |
pIC50
8.8
(IC50 1.5x10-9 M)
[77]
Description: Inhibition of kinase activity
|
almonertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.7
|
pIC50 |
97 |
|
⤷ |
pIC50
8.7
(IC50 1.89x10-9 M)
[97]
Description: Inhibition of wild type EGFR enzyme activity in a TR-FRET assay
|
AEE788
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.7
|
pIC50 |
82 |
|
⤷ |
pIC50
8.7
(IC50 2x10-9 M)
[82]
|
afatinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.0 – 9.3
|
pIC50 |
21,49 |
|
⤷ |
pIC50
8.0 – 9.3
(IC50 1.1x10-8 – 5x10-10 M)
[21,49]
|
CUDC-101
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.6
|
pIC50 |
12 |
|
⤷ |
pIC50
8.6
(IC50 2.4x10-9 M)
[12]
|
compound 17b [PMID: 35286086]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.6
|
pIC50 |
1 |
|
⤷ |
pIC50
8.6
(IC50 2.5x10-9 M)
[1]
|
pelitinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.8 – 9.2
|
pIC50 |
90-91 |
|
⤷ |
pIC50
7.8 – 9.2
(IC50 1.45x10-8 – 6x10-10 M)
[90-91]
|
falnidamol
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.5
|
pIC50 |
78 |
|
⤷ |
pIC50
8.5
(IC50 3x10-9 M)
[78]
|
PKI166
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.4
|
pIC50 |
44 |
|
⤷ |
pIC50
8.4
(IC50 3.7x10-9 M)
[44]
|
JAK3 inhibitor II
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.4
|
pIC50 |
17 |
|
⤷ |
pIC50
8.4
(IC50 4x10-9 M)
[17]
|
sapitinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.4
|
pIC50 |
9 |
|
⤷ |
pIC50
8.4
(IC50 4x10-9 M)
[9]
|
zipalertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.1 – 8.7
|
pIC50 |
36 |
|
⤷ |
pIC50
8.7
(IC50 2x10-9 M)
[36]
Description: Inhibition of hEGFR with T790M/L858R mutation in a biochemical enzyme assay
pIC50
8.1
(IC50 7.4x10-9 M)
[36]
Description: Inhibition of hEGFR with D770_N771insNPG insertion in a biochemical enzyme assay
pIC50
8.1
(IC50 8x10-9 M)
[36]
Description: Inhibition of WT hEGFR in a biochemical enzyme assay
|
BMS-690514
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.3
|
pIC50 |
58 |
|
⤷ |
pIC50
8.3
(IC50 5x10-9 M)
[58]
|
ibrutinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.3
|
pIC50 |
11 |
|
⤷ |
pIC50
8.3
(IC50 5.3x10-9 M)
[11]
|
AG1478
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.2
|
pIC50 |
83 |
|
⤷ |
pIC50
8.2
(IC50 6x10-9 M)
[83]
|
dacomitinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.2
|
pIC50 |
8 |
|
⤷ |
pIC50
8.2
(IC50 6x10-9 M)
[8]
|
compound 38 [PMID: 24915291]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.1
|
pIC50 |
52 |
|
⤷ |
pIC50
8.1
(IC50 7x10-9 M)
[52]
|
abivertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.1
|
pIC50 |
95 |
|
⤷ |
pIC50
8.1
(IC50 7.68x10-9 M)
[95]
Description: In a biochemical assay.
|
poziotinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.1
|
pIC50 |
61 |
|
⤷ |
pIC50
8.1
(IC50 8x10-9 M)
[61]
|
lapatinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.0
|
pIC50 |
76 |
|
⤷ |
pIC50
8.0
(IC50 1.02x10-8 M)
[76]
|
ZM-306416
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
8.0
|
pIC50 |
4 |
|
⤷ |
pIC50
8.0
(IC50 1x10-8 M)
[4]
|
pyrotinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Irreversible inhibition
|
7.9
|
pIC50 |
51 |
|
⤷ |
pIC50
7.9
(IC50 1.3x10-8 M)
[51]
|
selatinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.9
|
pIC50 |
99 |
|
⤷ |
pIC50
7.9
(IC50 1.3x10-8 M)
[99]
|
dosimertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.9 – 8.8
|
pIC50 |
60 |
|
⤷ |
pIC50
8.8
(IC50 1.7x10-9 M)
[60]
Description: Enzymatic inhibitory activity vs. L858R/T790M EGFR
pIC50
6.9
(IC50 1.138x10-7 M)
[60]
Description: Enzymatic inhibitory activity vs. WT EGFR
|
PD 158780
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.8
|
pIC50 |
73 |
|
⤷ |
pIC50
7.8
(IC50 1.5x10-8 M)
[73]
Description: Inhibition of EGFR autophosphorylation
|
BLU945
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
>7.8
|
pIC50 |
13 |
|
⤷ |
pIC50
>7.8
(IC50 <1.5x10-8 M)
[13]
Description: Biochemical enzyme inhibition assay (measuring inhibition of peptide substrate phosphorylation) using EGFR with triple mutation (del 19 or exon 21 L858R substitution mutation, T790M mutation, and C797S mutation)
|
compound 52 [PMID: 36749735]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.6 – 7.8
|
pIC50 |
50 |
|
⤷ |
pIC50
7.8
(IC50 1.5x10-8 M)
[50]
Description: Inhibition of EGFRL858R/T790M enzyme activity
pIC50
7.6
(IC50 2.5x10-8 M)
[50]
Description: Inhibition of WT EGFR enzymatic activity
|
EGFR/ErbB-2 inhibitor
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.7
|
pIC50 |
20 |
|
⤷ |
pIC50
7.7
(IC50 2x10-8 M)
[20]
|
lazertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
>7.7
|
pIC50 |
79 |
|
⤷ |
pIC50
>7.7
(IC50 <2x10-8 M)
[79]
Description: Measuring inhibition of mutant EGFR kinase activities in biochemical assays (equivalent potency against Del19, L858R, L858R/T790M and Del19/T790M EGFR mutants). NOTE lazertinib is inactive vs. wild type EGFR.
|
EGFR inhibitor
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.7
|
pIC50 |
24 |
|
⤷ |
pIC50
7.7
(IC50 2.1x10-8 M)
[24]
|
lifirafenib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.5
|
pIC50 |
80 |
|
⤷ |
pIC50
7.5
(IC50 2.9x10-8 M)
[80]
Description: Inhibition of wild type EGFR kinase domain (aa669-1210)
|
compound 6g [PMID: 30633509]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.5
|
pIC50 |
75 |
|
⤷ |
pIC50
7.5
(IC50 3x10-8 M)
[75]
|
BMS-599626
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.5
|
pIC50 |
29 |
|
⤷ |
pIC50
7.5
(IC50 3.2x10-8 M)
[29]
|
AZ5104
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.5
|
pIC50 |
18 |
|
⤷ |
pIC50
7.5
(IC50 3.3x10-8 M)
[18]
Description: Inhibition of wild type EGFR phosphorylation in human LoVo cells
|
icotinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.3
|
pIC50 |
38 |
|
⤷ |
pIC50
7.3
(IC50 4.5x10-8 M)
[38]
Description: Inhibition of EGFR-mediated intracellular tyrosine phosphorylation in EGF-stimulated human A431 cells.
|
DBPR112
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.3
|
pIC50 |
54 |
|
⤷ |
pIC50
7.3
(IC50 4.8x10-8 M)
[54]
Description: Enzymatic activity inhibition of EGFRL858R/T790M
|
sunvozertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.1
|
pIC50 |
53 |
|
⤷ |
pIC50
7.1
(IC50 8.04x10-8 M)
[53]
Description: Inhibition of WT EGFR phosphorylation in A431 cells
|
neratinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.0
|
pIC50 |
71 |
|
⤷ |
pIC50
7.0
(IC50 9.2x10-8 M)
[71]
Description: Inhibition of autophosphorylation of the cytoplasmic domain of the RTK in a cell free system.
|
mobocertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
7.0
|
pIC50 |
39 |
|
⤷ |
pIC50
7.0
(IC50 1x10-7 M)
[39]
Description: Inhibition of EGFR harbouring concurring exon 21, L858R and T790M mutations.
|
AG 112
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.9
|
pIC50 |
31 |
|
⤷ |
pIC50
6.9
(IC50 1.25x10-7 M)
[31]
Description: Measuring inhibition of substrate phosphorylation.
|
brigatinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.9
|
pIC50 |
45 |
|
⤷ |
pIC50
6.9
(IC50 1.29x10-7 M)
[45]
|
PF-670462
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.8
|
pIC50 |
7 |
|
⤷ |
pIC50
6.8
(IC50 1.5x10-7 M)
[7]
Description: In a biochemical kinase assay.
|
PP1
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.6
|
pIC50 |
34 |
|
⤷ |
pIC50
6.6
(IC50 2.5x10-7 M)
[34]
|
PP121
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.6
|
pIC50 |
5 |
|
⤷ |
pIC50
6.6
(IC50 2.6x10-7 M)
[5]
|
BI-4142
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.6
|
pIC50 |
89 |
|
⤷ |
pIC50
6.6
(IC50 2.7x10-7 M)
[89]
Description: Inhibition of autophosphorylation of WT EGFR overexpressed in HEK293 cells
|
vandetanib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.5
|
pIC50 |
15 |
|
⤷ |
pIC50
6.5
(IC50 3x10-7 M)
[15]
|
mavelertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.5
|
pIC50 |
69 |
|
⤷ |
pIC50
6.5
(IC50 3.07x10-7 M)
[69]
|
olmutinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.0 – 7.0
|
pIC50 |
16 |
|
⤷ |
pIC50
6.0 – 7.0
(IC50 1x10-6 – 1x10-7 M)
[16]
Description: Biochemical assay
|
tuxobertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.3 – 6.5
|
pIC50 |
25 |
|
⤷ |
pIC50
6.3 – 6.5
(IC50 5x10-7 – 3x10-7 M)
[25]
Description: Inhibition of WT EGFR kinase activity
|
AG 490
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.4
|
pIC50 |
30 |
|
⤷ |
pIC50
6.4
(IC50 4x10-7 M)
[30]
Description: Inhibition of substrate phosphorylation.
|
tucatinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.3
|
pIC50 |
48 |
|
⤷ |
pIC50
6.3
(IC50 4.49x10-7 M)
[48]
Description: Inhibition of enzyme activity in a biochemical assay.
|
osimertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.3
|
pIC50 |
87 |
|
⤷ |
pIC50
6.3
(IC50 4.94x10-7 M)
[87]
|
compound 19a [PMID: 30503936]
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.3
|
pIC50 |
70 |
|
⤷ |
pIC50
6.3
(IC50 5.2x10-7 M)
[70]
|
zongertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
6.2
|
pIC50 |
88 |
|
⤷ |
pIC50
6.2
(IC50 5.79x10-7 M)
[88]
Description: Inhibition of wild type EGFR phosphorylation
|
acalabrutinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
<6.0
|
pIC50 |
11 |
|
⤷ |
pIC50
<6.0
(IC50 >1x10-6 M)
[11]
|
dovitinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
5.7
|
pIC50 |
84 |
|
⤷ |
pIC50
5.7
(IC50 2x10-6 M)
[84]
|
orantinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
<4.0
|
pIC50 |
43 |
|
⤷ |
pIC50
<4.0
(IC50 >1x10-4 M)
[43]
|
naquotinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
-
|
- |
59 |
|
⤷ |
[59]
|
tarloxotinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
-
|
- |
68 |
|
⤷ |
[68]
|
furmonertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
-
|
- |
56 |
|
⤷ |
[56]
|
rezivertinib
|
|
|
|
|
|
|
|
|
|
|
Hs |
Inhibition
|
-
|
- |
67 |
|
⤷ |
[67]
|