Refametinib (RDEA119, Bay 86-9766)
Refametinib (RDEA119, Bay 86-9766) is a potent, ATP non-competitive and highly selective inhibitor of MEK1 and MEK2 with IC50 of 19 nM and 47 nM, respectively.
MEK162 (ARRY-162, ARRY-438162)
MEK162 (ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM. Phase 1.
Sorafenib is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively.
Trametinib (GSK1120212) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2.
Features:More potent than PD0325901 or AZD6244.
Selumetinib (AZD6244) is a potent, highly selective MEK1 inhibitor with IC50 of 14 nM, also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Phase 3.
Features:First MEK inhibitor being tested in Phase II clinical trials.
PD0325901 (PD325901) is selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2.
U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059.
Features:A chemically synthesized and highly selective inhibitor of both MEK1 and MEK2.
PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2.
Features:Does not inhibit c-Raf phosphorylated MEK1.
Pimasertib (AS-703026) is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2 with IC50 of 5 nM-2 μM in MM cell lines. Phase 2.
Features:A novel, highly selective and potent allosteric inhibitor of MEK1/2.
BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM, also inhibits ERK5 catalytic activity with IC50 of 59 nM, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2.