MEK1 Inhibitor

PD318088 is a potent, allosteric and non-ATP competitive MEK1/2 inhibitor, an analog of PD184352 (HY-50295). PD318088 binds simultaneously with ATP in a region of the MEK1 active site that is adjacent to the ATP-binding site. PD318088 can be used for cancer research.

Cobimetinib hemifumarate is a novel selective MEK1 inhibitor, and the IC₅₀ value against MEK1 is 4.2 nM.

RO4987655 is an orally active and highly selective MEK inhibitor with an IC₅₀ of 5.2 nM for inhibition of MEK1/MEK2.

MAP855 is a highly potent, selective, ATP-competitive and orally active MEK1/2 kinase inhibitor (MEK1 ERK2 cascade IC₅₀=3 nM, pERK EC₅₀=5 nM). MAP855 shows equipotent inhibition of wild-type and mutant MEK1/2.

RGB-286638 free base is a potent inhibitor of CDK and MAPK9. RGB-286638 free base 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 free base inhibits GSK-3β and TAK1, with IC₅₀ values of 3 nM and 5 nM, respectively. RGB-286638 free base induces caspase-dependent Apoptosis in cells. RGB-286638 free base delays tumor growth in an orthotopic glioblastoma mouse model. RGB-286638 free base extends survival in multiple myeloma models. RGB-286638 free base can be used in research related to glioblastoma and multiple myeloma.

N-trans-feruloyloctopamine is a natural hydroxycinnamic acid amide compound derived from garlic outer skin, possessing tyrosinase inhibition, FGF2 inhibition, anti-melanogenic, and anti-tumor activities. N-trans-feruloyloctopamine inhibits tyrosinase activity and downregulates tyrosinase mRNA and protein expression (IC₅₀ = 5.3 μM), and inhibits melanogenesis in α-MSH-stimulated B16F10 cells. N-trans-feruloyloctopamine inhibits Akt and p38 MAPK phosphorylation, binds to E-cadherin to block EMT, reduces Slug, inhibits hepatocellular carcinoma invasion, and induces hepatocellular carcinoma cell apoptosis. N-trans-feruloyloctopamine can be used in research related to hepatocellular carcinoma, pigmentation disorders, and UVB-induced skin damage.

Lixisenatide acetate is a glucagon-like peptide-1 (GLP-1) receptor agonist. Lixisenatide acetate inhibits the inflammatory response through down regulation of pro-inflammatory cytokines, and suppresses of the Akt-MEK1/2 signaling pathway. Lixisenatide acetate can inhibit oxidative stress, mitochondrial dysfunction and apoptosis. Lixisenatide acetate 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.

Cucurbitacin IIa (Hemslecin A) is an orally active, blood-brain barrier-permeable EGFR inhibitor with an IC₅₀ of 1.455 nM against human EGFR. Cucurbitacin IIa induces caspase-3-dependent apoptosis, downregulates survivin expression, enhances autophagy levels, disrupts the actin cytoskeleton via actin aggregation, arrests the cell cycle at the G2/M phase, and exerts anti-inflammatory activity by inhibiting the EGFR-MAPK signaling pathway. Cucurbitacin IIa can be used in the research of inflammation-related diseases, depression, and cancers such as non-small cell lung cancer.

Hypothemycin, a fungal polyketide, is a multikinase inhibitor with K_is of 10/70 nM, 17/38 nM, 90 nM, 900 nM/1.5 μM, and 8.4/2.4 μM for VEGFR2/VEGFR1, MEK1/MEK2, FLT-3, PDGFRβ/PDGFRα, and ERK1/ERK2, respectively.

Nedometinib (NFX-179) is a specific MEK1 inhibitor with an IC₅₀ of 135 nM. Nedometinib inhibits p-ERK, MAPK. Nedometinib exerts anticancer activity against squamous cell carcinoma. Nedometinib can be used for research in dermatosis, neurofibromatosis.

PD-334581 is a MEK1 inhibitor.

CHMFL-EGFR-202 is a potent, irreversible inhibitor of epidermal growth factor receptor (EGFR) mutant kinase, with IC₅₀s of 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases, respectively. CHMFL-EGFR-202 exhibits ～10-fold selectivity for EGFR L858R/T790M against the EGFR wild-type in cells. CHMFL-EGFR-202 adopts a covalent “DFG-in-C-helix-out” inactive binding conformation with EGFR, with strong antiproliferative effects against EGFR mutant-driven nonsmall-cell lung cancer (NSCLC) cell lines.

DS03090629 is an orally active, ATP-competitive MEK1/2 inhibitor. DS03090629 binds to the ATP-binding pocket of MEK, and this binding is unaffected by phosphorylation status. DS03090629 exhibits high affinity for both MEK and phosphorylated MEK, with K_d values of 0.11 nM and 0.15 nM, respectively. DS03090629 inhibits the MEK1^F53L mutant while retaining activity relative to wild-type MEK1. DS03090629 suppresses the MAPK pathway, cell proliferation, and BRAF overexpression-mediated drug resistance in melanoma cells. DS03090629 can be used for research related to melanoma.

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.

(S)-N-trans-feruloyloctopamine is an isomer of N-trans-feruloyloctopamine (HY-N2232). N-trans-feruloyloctopamine is a natural hydroxycinnamic acid amide compound derived from garlic husk, possessing tyrosinase inhibitory, FGF2 inhibitory, anti-melanogenic, and anti-tumor activities, and is used in research related to hepatocellular carcinoma, pigmentation disorders, and UVB-induced skin damage.

MEK-IN-7 (compound WX086) is potent, orally active and selective MEK inhibitor (MEK1 IC₅₀ = 29.62 nM). MEK-IN-7 inhibits HT29 and A375 cell proliferation with IC₅₀s of 0.62 and 0.40 nM. MEK-IN-7 inhibits tumor growth in a HL-29 xenograft mouse model. MEK-IN-7 can be used for melanoma and colon cancer research.

RO5068760 is a potent, orally active and selective non-ATP-competitive MEK1/2 inhibitor with an IC₅₀ of 0.025 μM for MEK1. RO5068760 significantly inhibits MAPK pathway activity, thereby inducing G1 cell cycle arrest and apoptosis to inhibit cancer cell growth. RO5068760 exhibits significant efficacy in a broad spectrum of tumors with aberrant MAPK pathway activation. RO5068760 can be used for melanoma, colorectal cancer, non-small cell lung cancer (NSCLC), and pancreatic cancer research.

AKT1-IN-13 is an orally active AKT1 inhibitor with an IC₅₀ of 5.17 μM. AKT1-IN-13 also exhibits high inhibitory activity against PAK1, PKA, MAP2K1 (MEK1 / MAPKK1) and MAPK1 (ERK2). AKT1-IN-13 induces cell apoptosis, activates the pro-apoptotic protein BAX, inhibits the anti-apoptotic protein Bcl-2, and activates caspase 3 simultaneously. As a cytotoxic agent, AKT1-IN-13 exerts a killing effect on orthotopically transplanted liver cancer in an AKT1-dependent manner. AKT1-IN-13 can be used in studies related to hepatocellular carcinoma.

MEK/RAF-IN-1 (Compound 16b) is an inhibitor of both MEK and RAF. It shows potent inhibition with IC₅₀ values of 28 nM for MEK1, and 3 nM each for BRAF and BRAFV600E. MEK/RAF-IN-1 demonstrates significant antitumor activity, effectively inhibiting cell proliferation in vitro against MIA PaCa-2 (G12C KRAS), HCT116 (G13D KRAS), and C26 (G12D KRAS) cells. Additionally, it inhibits tumor growth in xenograft mouse models of colorectal cancer.

MEK/PI3K-IN-2 (compound 6s) is a potent MEK/PI3K inhibitor, with IC₅₀ values of 352 nM (MEK1), 107 nM (PI3Kα), and 137 nM (PI3Kδ), respectively. MEK/PI3K-IN-2 suppresses pAKT and pERK1/2 levels. MEK/PI3K-IN-2 shows anti-proliferative activity against tumor cell lines.