Selumetinib (AZD6244) is selective, non-ATP-competitive oral MEK1/2 inhibitor, with an IC50 of 14 nM for MEK1. Selumetinib (AZD6244) inhibits ERK1/2 phosphorylation.

PD0325901-O-C2-dioxolane has main portion of MEK inhibitor PD0325901. PD0325901-O-C2-dioxolane and a ligand of VHL or CRBN E3 ligase can be used in the synthesis of MEK1/2 degrader.

Zapnometinib (PD0184264), an active metabolite of CI-1040, is a MEK inhibitor, with an IC50 of 5.7 nM. Zapnometinib exhibits antiviral activity against influenza virus and antibacterial activities.

MEK4 inhibitor-1 is a novel MEK4 inhibitor against pancreatic adenocarcinoma with an IC50 value of 61 nM.

MEK4 inhibitor-2 is a novel MEK4 inhibitor against pancreatic adenocarcinoma with an IC50 value of 83 nM.

PD-334581 is a MEK1 inhibitor.

(R)-STU104 is a potent, first-in-class TAK1-MKK3 porotein-protein interaction (PPI) inhibitor with SPR Kd of 71 nM for binding MKK3, disrupting the TAK1 phosphorylating MKK3.(R)-STU104 exhibited the potent inhibitory activity on TNF-α production on RAW264.7 cells with IC50 of 0.58 uM, suppressed the TAK1/MKK3/p38/MnK1/MK2/elF4E signal pathways.(R)-STU104 demonstrated remarkable dose-effect relationships on both acute and chronic mouse ulcerative colitis (UC) models.(R)-STU104 showed better anti-UC efficacy in vivo at 10 mg/kg/d than mesalazine at the dose of 50 mg/kg/d.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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).

HRX-0233 (HRX0233) is a potent, selective MAP2K4 (MKK4) inhibitor, HRX-0233 is synergistic with RAS inhibitors in KRAS-mutant cancers.

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.

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