Table 1. Distributions of the Binding Modes for FDA-Approved Kinase-Targeted Drugs^a.

approved inhibitor	approved year	PDB entry	involved clusters for the binding modes								inhibitor of type
			1	2	3	4	5a	5b	5c	5d
IMATINIB	2001	4BKJ	√	√	√		√				II
GEFITINIB	2003	4I22	√	√			√	√		√	I
ERLOTINIB	2004	4HJO	√	√			√	√		√	I
SORAFENIB	2005	4ASD	√	√	√		√	√			II
DASATINIB	2006	3QLG		√			√	√		√	I
SUNITINIB	2006	2Y7J					√			√	I
NILOTINIB	2007	3GP0	√	√	√√		√				II
LAPATINIB	2007	1XKK	√				√	√		√	I
PAZOPANIB	2009	2X9F	√				√	√		√	I
VANDETANIB	2011	2IVU	√				√	√		√	I
RUXOLITINIB	2011	3VS7		√			√				I
CRIZOTINIB	2011	3ZBF					√	√	√	√	I
VEMURAFENIB	2011	3OG7		√			√	√			I
TOFACITINIB	2012	3LXN					√	√	√		I
BOSUTINIB	2012	4OTW	√				√	√		√	I
CABOZANTINIB	2012	3U6J		√	√		√	√			II
PONATINIB	2012	4C8B		√	√	√	√				II
REGORAFENIB	2012	3WZE	√	√			√	√			II
AXITINIB	2012	4AGC		√			√			√	I
IBRUTINIB	2013	4IFG	√				√	√			I
AFATINIB	2013	4G5J					√		√	√	I
TRAMETINIB	2013	3PP1	√	√	√				√		III
DABRAFENIB	2013	4CQE	√	√			√	√	√		I
NINTEDANIB	2014	3C7Q	√				√	√		√	I
IDELALISIB	2014	4XE0					√			√	I
CERITINIB	2014	4MKC		√			√	√		√	I
PALBOCICLIB	2015	2EUF		√			√	√		√	I
LENVATINIB	2015	3WZD		√	√		√			√	II
COBIMETINIB	2015	4AN2	√	√	√				√		III
OSIMERTINIB	2015	4ZAU					√	√	√	√	I

^aThe “√” means the interaction exists in the corresponding regions of the binding pocket (Figure 8i).