MEK1 Inhibitor

Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib activates autophagy and induces apoptosis, cross the blood-brain barrier (BBB), used in research related to subarachnoid hemorrhage (SAH).

Mirdametinib (PD0325901) is an orally active, selective and non-ATP-competitive MEK inhibitor with an IC₅₀ of 0.33 nM. Mirdametinib exhibits a K_i^app of 1 nM against activated MEK1 and MEK2. Mirdametinib suppresses the expression of p-ERK1/2 and induces apoptosis. Mirdametinib has anti-cancer activity for a broad spectrum of human tumor xenografts.

U0126 is a potent, non-ATP competitive and selective MEK1 and MEK2 inhibitor, with IC₅₀s of 72 nM and 58 nM, respectively. U0126 is an autophagy and mitophagy inhibitor.

PD98059 is a potent and selective MEK inhibitor with an IC₅₀ of 5 µM. PD98059 binds to the inactive form of MEK, thereby preventing the activation of MEK1 (IC₅₀ of 2-7 µM) and MEK2 (IC₅₀ of 50 µM) by upstream kinases. PD98059 is a ERK1/2 signaling inhibitor. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR), and suppresses TCDD binding (IC₅₀ of 4 μM) and AHR transformation (IC₅₀ of 1 μM). PD98059 also inhibits Mycobacterium bovis Bacillus CalmetteGuerin (BCG)-induced autophagy.

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. Selumetinib can penetrate the blood brain barrier (BBB).

Refametinib (BAY 869766; RDEA119) is an orally available, potent, non-ATP-competitive, selective, allosteric MEK1/MEK2 inhibitor with IC₅₀s of 19 nM and 47 nM, respectively.

RGB-286638 is a potent inhibitor of CDK and MAPK9. RGB-286638 inhibits the activities of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3 and p35-CDK5, with IC₅₀ values of 1, 2, 3, 4, 5 and 5 nM, respectively. RGB-286638 inhibits GSK-3β and TAK1, with IC₅₀ values of 3 nM and 5 nM, respectively. RGB-286638 induces caspase-dependent Apoptosis in cells. RGB-286638 delays tumor growth in an orthotopic glioblastoma mouse model. RGB-286638 extends survival in multiple myeloma models. RGB-286638 can be used in research related to glioblastoma and multiple myeloma.

Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK1 inhibitor with an IC₅₀ of 4.2 nM for MEK1.

U0126 (U0126-EtOH) is a potent, non-ATP competitive and selective MEK1 and MEK2 inhibitor, with IC₅₀s of 72 nM and 58 nM, respectively. U0126 is an autophagy and mitophagy inhibitor.

Isorhamnetin is a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L.. Isorhamnetin suppresses skin cancer through direct inhibition of MEK1 and PI3K.

Trametinib (DMSO solvate) (GSK-1120212 (DMSO solvate)) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib (DMSO solvate) activates autophagy and induces apoptosis. This product is in solid form, a DMSO solvate, and a stable crystalline form.

CI-1040 (PD 184352) is an orally active, highly specific, small-molecule inhibitor of MEK with an IC₅₀ of 17 nM for MEK1.

Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist. Lixisenatide inhibits the inflammatory response through down regulation of pro-inflammatory cytokines, and suppresses of the Akt-MEK1/2 signaling pathway. Lixisenatide can inhibit oxidative stress, mitochondrial dysfunction and apoptosis. Lixisenatide can be used for the researches of inflammation, metabolic disease, neurological disease and cardiovascular disease, such as rheumatoid arthritis, diabetes, Alzheimer's disease and atherosclerosis.

Tunlametinib is a highly selective, orally active MEK1/2 inhibitor (IC₅₀=1.9 nM, MEK1). Tunlametinib blocks the RAS-RAF-MEK-ERK signaling pathway, arrests tumor cell cycle and promotes apoptosis. Tunlametinib potently inhibits the proliferation of RAS/RAF mutant cancer cells (such as BRAF V600E, KRAS G12C mutant cells). Tunlametinib shows synergistic anti-tumor effects with BRAF/KRASG12C/SHP2 inhibitors, Docetaxel (HY-B0011). Tunlametinib can be used to study targeted therapy for RAS/RAF mutation-driven malignancies (such as melanoma, colorectal cancer, and non-small cell lung cancer).

Pimasertib (AS703026) is a highly selective, ATP non-competitive allosteric orally available MEK1/2 inhibitor.

GDC-0623 (RG 7421) is a potent, ATP-uncompetitive inhibitor of MEK1 (K_i=0.13 nM, +ATP), and displays 6-fold weaker potency against HCT116 (KRAS (G13D), EC₅₀=42 nM) versus A375 (BRAF^V600E, EC₅₀=7 nM).

Trametiglue, a derivative of Trametinib (HY-10999), targets both KSR-MEK and RAF-MEK with unprecedented potency and selectivity via unique interfacial binding interactions.

Azelnidipine (CS 905) is a dihydropyridine calcium channel blocker that is effective orally. Azelnidipine inhibits the intracellular calcium ion flow and lower blood pressure by selectively blocking L-type calcium channel on the membrane of vascular smooth muscle. Azelnidipine inhibits esophageal squamous cell carcinoma proliferation by targeting MEK1/2. Azelnidipine also has anti-inflammatory, antioxidant and neuroprotective effects .

AZD8330 (ARRY-424704) is a potent, uncompetitive MEK1/MEK2 inhibitor, with an IC₅₀ of 7 nM.

SL327 inhibits MEK1 and MEK2, with IC₅₀ values of 180 nM and 220 nM, respectively.