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. Author manuscript; available in PMC: 2024 Apr 27.
Published in final edited form as: Methods Enzymol. 2023 Apr 27;685:171–198. doi: 10.1016/bs.mie.2023.03.013

Table 2.

Structurally characterized fourth-generation EGFR inhibitors targeting C797S mutants.

Compound Namea PDB ID EGFR Kinase Domain αC-helix Interactions with K745 and D855 Ref
1 LN2057 6V6K out H-bond between imidazole and K745 (David E Heppner, Günther, Wittlinger, Laufer, & Eck, 2020)
2 6VHN in none (David E Heppner et al., 2020)
3 LN2899 6V66 out H-bond between imidazole and K745 (David E Heppner et al., 2020)
4 6VHP in none (David E Heppner et al., 2020)
5 LN2380 6V6O out H-bond between imidazole and K745 (David E Heppner et al., 2020)
6 6VH4 in none (David E Heppner et al., 2020)
7 LN2084 6V5N out H-bond between imidazole and K745 (David E Heppner et al., 2020)
8 LN2725 6V5P out H-bond between imidazole and K745 (David E Heppner et al., 2020)
9 AP-26113 (Brigatinib) 7AEM in H-bond between phosphine oxide and K745 (Floch, Finlay, Bianco, Bickerton, Colclough, Cross, Cuomo, Guerot, Hargreaves, & Martin, 2019; Uchibori et al., 2017a)
10 BI-4020 7KY0 out H-bond between pyrazole oxide and K745 (Tyler S. Beyett, Rana, et al., 2022)
11 7KXZ in H-bond between pyrazole oxide and K745 (Tyler S Beyett, Jaimin K Rana, Ilse K Schaeffner, David E Heppner, & Michael J Eck, 2022)
12 Compound 7 (Related to BLU-945) (2) 8D73 In H-bond between alcohol and K745 (Eno et al., 2022)
13 Compound 24 (Related to BLU-945) (3) 8D76 in H-bond between alcohol and K745 (Eno et al., 2022)
14 LS_2_40 7ER2 in H-bond between phosphine oxide and K745 (S. Li, Zhang, Zhu, Lei, Lai, Peng, Tong, Pang, Lu, & Ding, 2022)
15 Compound 10 (4) 7AEI in H-bond between phosphine oxide and K745 (Finlay et al., 2021; Floch, Finlay, Bianco, Bickerton, Colclough, Cross, Cuomo, Guerot, Hargreaves, & Martin, 2019)
16 CH7233163 6LUB in H-bond between pyrazole and K745 (Kashima et al., 2020)
17 Compound 1 (5) 5C8K in H-bond between methoxy and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
18 Compound 17 (6) 5C8M in H-bond between sulfone oxygen and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
19 Compound 23 (7) 5C8N in H-bond between amin and D855, H-bond between methoxy and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
20 Compound 24 (8) 5CAL in H-bond between K745 and E762 in αC-helix (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
21 Compound 27 (9) 5CAN in H-bond between K745 and E762 in αC-helix in and interact with D855 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
22 Compound 29 (10) 5CAO in H-bond between sulfone oxygen and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
23 Compound 30 (11) 5CAP in H-bond between sulfone oxygen and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
24 Compound 33 (12) 5CAQ in H-bond between methoxy and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
25 Compound 41a (13) 5CAV in H-bond between methoxy and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
26 5CAS in H-bond between methoxy and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
27 Compound 41b (14) 5CAU in H-bond between methoxy and K745 (Heald, Bowman, Bryan, Burdick, Chan, Chan, Chen, Clausen, Dominguez-Fernandez, & Eigenbrot, 2015)
a

Note that we have listed all compounds according to their generic name or compound code included in the original reference. We have elected to enumerate all compounds here that are reported by numeral in the original reference for clarity.