. Author manuscript; available in PMC: 2022 Feb 3.

Published in final edited form as: J Med Chem. 2021 Oct 14;65(2):1525–1535. doi: 10.1021/acs.jmedchem.1c01186

Table 1.

Summary of kinases with a FP Ncap or Ncap+2 Cys and the covalent inhibitors^a directed at the location

Kinase	Family	Group	PDB	Residue	PROPKA^b	TCKI
FP Ncap Cys
BTK	Tec	TK	3pj3	C481	9.6	ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib,⁹ orelabrutinib¹⁰
BMX	Tec	TK	3sxs	C496	9.9	ibrutinib
TEC	Tec	TK	4hct^a	C449	9.2	ibrutinib, ritlecitinib^c
ITK	Tec	TK	3miy	C442	10.7	ibrutinib
TXK	Tec	TK	3t9t^a	C350	10.4	acalabrutinib
BLK	Src	TK	4mxy^a	C319	10.6	ibrutinib, acalabrutinib
JAK3	JakA	TK	5lwm	C909	10.3	ritlecitinib¹¹
EGFR	EGFR	TK	4zjv	C797	11.4	afatinib, osimertinib, dacomitinib, neratinib, olmutinib,¹² pyrotinib,¹³ mobocertinib,¹⁴ ibrutinib, acalabrutinib
ERBB2	EGFR	TK	3pp0	C805	10.8	acalabrutinib
ERBB4	EGFR	TK	2r4b	C803	11.0	ibrutinib
MKK7	STE7	STE	6qfr	C218	9.1	investigational inhibitors^15,16
FP Ncap+2 Cys
JNK1	MAPK	CMGC	2xrw	C116	10.0	investigational inhibitors¹⁷
JNK2	MAPK	CMGC	3e7o	C116	10.2	investigational inhibitors¹⁷
JNK3	MAPK	CMGC	6emh	C154	10.4	investigational inhibitors¹⁸
CASK	CASK	CAMK	3mfr	C100	13.0	unkown

Inhibitors without references are from the FDA approved ones from the FDA Orange Book (https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm). Those with references are in the last stage of clinical trial; some of them have gained regulatory approval in foreign countries.

PROPKA calculations were performed with PROPKA3.¹⁹

Template structure used for homology modeling with SWISS-MODEL.²⁰