. 2023 Oct 20;13(10):1555. doi: 10.3390/biom13101555

Table 3.

List of representative allosteric or ATP-competitive MEK inhibitors. Some of the earliest inhibitors present major off-target effects, such as PD98059 and U0126 [445]. Among the most selective is PD0325901. The two values MEK1 and MEK2, respectively. (ND = not determined).

Name	IC₅₀	Type	Target	Reported	Reference
PD98059	2–7 µM 50 µM	non-ATP-competitive	MEK1/2	1995	[446,447]
U0126	72 nM 58 nM	non-ATP-competitive	MEK1/2	1998	[448,449]
CI-1040/ PD184352	17 nM	non-ATP-competitive	MEK1	1999	[450,451]
Mirdametinib/PD0325901	0.33 nM	non-ATP-competitive	MEK1/2	2004	[451,452]
PD184161	10–100 nM	non-ATP-competitive	MEK1/2	2006	[453]
Binimetinib/ MEK162 (MEKTOVI)	12 nM	non-ATP-competitive	MEK1/2	2006 (FDA-approved: 2018)	[454]
Selumetinib/AZD6244/ARRY-142886 (KOSELUGO)	14 nM	non-ATP-competitive	MEK1	2007 (FDA-approved: 2020)	[455]
Refametinib/RDEA-119/BAY 869766	19 nM 47 nM	non-ATP-competitive	MEK1/2	2009	[456]
RO4987655/CH4987655/ RG7167	5.2 nM	non-ATP-competitive	MEK1	2009	[457,458]
AZD8330/ARRY-704	7 nM	non-ATP-competitive	MEK1/2	2009	[459]
E6201	50 nM	ATP-competitive	MEK1	2009	[460]
Pimasertib/ AS703026/MSC1936369B	ND	non-ATP-competitive	MEK1/2	2010	[461]
WX-554/UCB1366554	4.7 nM 10.7 nM	non-ATP-competitive	MEK1/2	2010	[462]
RO5068760	25 nM	non-ATP-competitive	MEK1	2010	[463]
G-573	16 nM	non-ATP-competitive	MEK	2010	[464]
TAK-733	3.2 nM	non-ATP-competitive	MEK1/2	2011	[465]
CIP-137401	21 nM	non-ATP-competitive	MEK1	2011	[466]
Trametinib/GSK1120212/JTP-74057 (MEKINIST)	2 nM	non-ATP-competitive	MEK1/2	2011 (FDA-approved: 2013)	[467,468]
Avutometinib/RO5126766/ RG-7304/ CH-5126766, CKI-27, R-7304/VS-6766	8.2 nM 56 nM 160 nM 190 nM	non-ATP-competitive	BRAF^V600E CRAF MEK BRAF	2012	[469]
Cobimetinib/ GDC-0973 (COTELLIC)	4.2 nM	non-ATP-competitive	MEK1	2012 (FDA-approved: 2015)	[470]
G-894	13 nM	non-ATP-competitive	MEK1/2	2012	[471]
GDC-0623/RG 7421	0.13 nM	non-ATP-competitive	MEK1	2013	[472]
Tunlametinib/HL-085	1.9–10 nM	non-ATP-competitive	MEK1	2013	[473,474]
CZ0775	>10 μM	non-ATP-competitive	MEK1/2	2013	[475]
BI-847325	25/4 nM 25/15 nM	ATP-competitive	MEK1/2 Aurora kinase A/C	2015	[476]
EBI-1051	3.9 nM	non-ATP-competitive	MEK	2018	[477]
SC-1-151	26 nM	non-ATP-competitive	MEK1/2/5	2018	[478]
DPS-2	<5 µM	non-ATP-competitive	MEK/ERK PI3K/AKT	2019	[479]
KZ-001	7.4 nM	non-ATP-competitive	MEK1	2019	[480]
URML-3881	30 nM	non-ATP-competitive	MEK1/2	2019	[481]
FCN-159	8.8 nM	non-ATP-competitive	MEK1/2	2020	[482,483]
MAP855	3nM EC₅₀ 5 nM (pERK)	ATP-competitive	MEK1/2	2022	[484]
ABM-168	<30 nM	non-ATP-competitive	MEK1/2	2023	[485]
DS03090629	74 nM	ATP-competitive	MEK1/2	2023	[486]