Vacquinol-1 is an activator of MKK4-dependent macropinocytotic cell death in glioblastoma cells.

APS-2-79 is a novel modulator of KSR-dependent MAPK signalling,KSR2,IC50=120 nM

AZD6244 (Selumetinib, ARRY-142886) is highly potent to inhibit MEK1 with IC50 of 14 nM.

HRX-0233 (HRX0233) is a potent and selective inhibitor of MAP2K4 (MKK4), a kinase involved in the stress-activated protein kinase (SAPK) signaling pathway. MAP2K4 plays a role in regulating cellular responses to stress, apoptosis, and tumorigenesis. HRX-0233 has shown particular promise in KRAS-mutant cancers, where it exhibits synergistic effects with RAS inhibitors, making it a potential candidate for combination therapy in these difficult-to-treat cancers.

NFX-179 (Nedometinib, NFX179) is a potent, specific, topical, metabolically labile MEK1/2 inhibitor with biochemical IC50 of 135 nM (MEK1).

Darizmetinib (HRX-0215, HRX0215) is a potent, selective inhibitor of MKK4 (MAP2K4/SEK1), shows potential for promoting liver regeneration or reducing or preventing hepatocyte death.

GDC-0973 is a potent, highly selective inhibitor of mitogen-activated protein kinase kinase, also known as MEK, a serine/threonine kinase that is a component of the RAS/RAF/MEK/ERK pathway.

KZ-001 is a highly potent and selective MEK 1/2 inhibitor with IC50 values of 7.4/64 nM, respectively, exhibits greater inhibition against BRAF- and KRAS-mutant tumor cells than AZD6244.

DS03090629 is a potent, selective, ATP-competitive and orally available MEK1/2 inhibitor, shows high affinity for the MEK protein regardless of its phosphorylation status (npMEK (inactive) Kd=0.11 nM, and pMEK (active) Kd=0.15 nM).

DK2403 (DK-2403) is a highly potent, selective and covalent MAP2K7 (MEK7) inhibitor with IC50 of 10 nM, covalently engages the unique Cys218 residue within the active site.

INR119 is a small molecule allosteric MAPKK (MAP2K, MEK1/2) inhibitor, binds fission yeast homologue Wis1 near C458 and protects Wis1 from inactivation by low levels of H2O2 in vitro.INR119 pretreatment strongly potentiates the Wis1 response to low H2O2 in vivo.Phosphorylation of Sty1 depends entirely on activated Wis1, and the INR119-induced enhancement of Sty1 pathway activation upon H2O2 stress requires the upstream activation of Wis1 through the MAPKKKs.

OTS964 is a novel TOPK(T–lymphokine-activated killer cell–originated protein kinase) inhibitor.

Trametinib is a highly specific and potent MEK1 and MEK2 inhibitor with IC50 of 0.92 nM and 1.8 nM, respectively.

TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc.

RO4987655(CH-4987655) is an orally active small molecule, targeting mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1 IC50=5.2 nM), with potential antineoplastic activity.

PD0325901 (PD325901) is selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM.

BIX02188 is a selective inhibitor of MEK5 with IC50 of 4.3 nM, also inhibits ERK5 catalytic activity with IC50 of 810 nM, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2.

BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively. Phase 1.

AS703026(Pimasertib) is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2 with IC50 of 5 nM-2 μM in MM cell lines.

APS-2-79 is a novel modulator of KSR-dependent MAPK signalling,KSR2,IC50=120 nM

PD 98059 is a selective inhibitor of MEK and blocker of MAPK

U0124, an inactive U0126 analog, has no effect on c-Fos and c-Jun protein or mRNA levels. U0126 is a MEK inhibitor. U0124 does not inhibit MEK at concentrations up to 100 μM.

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.

U0126-EtOH(U-0126) 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 PD098059.

URML-3881 (URML3881) is a potent, specific MEK1/2 inhibitor IC50 of 30 nM in a cell-free kinase inhibition assay.URML-3881 shows no inhibition among a panel of other kinases including MEK 3 and MEK5, which are activated in alternative MAPK signaling pathways.URML-3881 reduces MAPK pathway activity in clear cell ovarian cancer (CCOC).URML-3881 causes reduced CCOC viability due to induction of tumor cell apoptosis and inhibition of proliferation.URML-3881 abrogates cisplatin-induced prosurvival MAPK signaling in CCOC, resulting in durable and dramatic tumor regression in vivo.

Tunlametinib is a benzoheterocyclic compound as MEK modulator with potential for treatment of cancer and inflammation.

MEK4 inhibitor 6ff is potent, selective MEK4 inhibitor with IC50 of 66 nM.MEK4 inhibitor 6ff displays excellent selectivity across the entire MEK family, 150-fold more potent against MEK4 than any other MEKkinase, and is at least 385-fold selective against three other MEK kinases.

MEK4 inhibitor 15o is potent, selective, cell permeable MEK4 inhibitor with IC50 of 83 nM.MEK4 inhibitor 10e demonstrated significant reduction of phospho-JNK and antiproliferative properties against pancreatic cancer cell lines, molecular inhibition of MEK4 pathway activates the MEK1/2 pathway.MEK4 inhibitor 10e demonstrated synergistic effects against pancreatic cancer cells with the combination of MEK1/2 inhibitors.

BT2 is a thermostable small-molecule inhibitor of vascular permeability and angiogenesis, interacts with MEK1 and inhibits ERK phosphorylation, FosB/ΔFosB, and VCAM-1 expression.BT2 blocks endothelial FosB/ΔFosB expression, proliferation, migration and wound repair after in vitro injury and network formation.BT2 also inhibited a range of other regulatory genes involved in cell proliferation, migration, angiogenesis, and inflammation including intercellular adhesion molecule-1 (ICAM-1), CXCL2, KLF5, Egr-1, and Fos.BT2 reduced retinal leakage in rats at least as effectively as aflibercept, a first-line therapy for nAMD/DR.

BSJ-04-122 is a potent, selective, covalent dual MKK4/7 inhibitor with IC50 of 4/181 nM, displays excellent kinome selectivity; BSJ-04-122 covalently targets a conserved cysteine (Cys247 for MKK4, and Cys261 for MKK7) located before the DFG motif. SJ-04-122 exhibits potent cellular target engagement and induces robust target-specific downstream effects. In breast cancer cell lines, BSJ-04-122 potently inhibited JNK phosphorylation, BSJ-04-122 significantly decreased levels of T183/Y185 pJNK at 5 uM, resulting in complete inhibition at 10 uM in MDA-MB-231 cells. The combination of the dual MKK4/7 inhibitor BSJ-04-122 with a selective, covalent JNK inhibitor (JNK-IN-8) demonstrated an enhanced antiproliferative activity against triple-negative breast cancer cells.