MEK

Trametinib (GSK1120212) is a MEK inhibitor that inhibits MEK1 and MEK2 (IC50=0.7 0.9 nM) with ATP non-competitive and oral activity. Trametinib activates autophagy and induces apoptosis.

SCH772984 is an ERK inhibitor that inhibits ERK1 and ERK2 (IC50=4 1 nM) and is highly selective and ATP-competitive. SCH772984 exhibits antitumor activity against BRAF or RAS mutant cells.

Mirdametinib (PD325901) is an MEK inhibitor (IC50=0.33 nM) with selective, non-ATP-competitive, and oral activity. Mirdametinib exhibits antitumor activity by inhibiting p-ERK1 2 expression and inducing apoptosis.

Cobimetinib (GDC-0973) is a MEK1 inhibitor (IC50=4.2 nM) with selective and oral activity. Cobimetinib exhibits antitumor activity, inhibiting tumor cell proliferation and inducing apoptosis.

PD98059 is an MEK inhibitor that inhibits MEK1 and MEK2 (IC50=2/50 μM) and is non-ATP-competitive. PD98059 is also antagonistic as a ligand for AHR. PD98059 inhibits autophagy.

Binimetinib (ARRY-162) is a MEK1 2 inhibitor (IC50=12 nM) with selective and oral activity. Binimetinib has antitumor activity for the treatment of metastatic melanoma that cannot be resected or has a BRAF V600E or V600K mutation.

PAF (C16) is a potent MAPK and MEK ERK activator that induces increased vascular permeability. PAF (C16) (PAF (C16)) is a platelet-activating factor, a phospholipid-derived mediator and a ligand for PAF G protein-coupled receptor (PAFR). PAF (C16) has shown anti-apoptotic and anti-inflammatory activity in vitro, inhibiting Caspase-dependent apoptosis by interacting with its receptor (PAF-R) to perform cell signaling.

Honokiol (NSC-293100) is the active principle of magnolia extract. It inhibits the activation of Akt and enhances the phosphorylation of ERK1 ERK2.

Selumetinib (AZD6244) is a MEK1 2 inhibitor that inhibits MEK1 (IC50=14 nM) with potent selectivity and is non-ATP-competitive. Selumetinib has antitumor activity and is used for the treatment of neurofibromatosis type 1 (NF1).

RO5126766 (CH5126766) is a dual RAF MEK inhibitor with IC50 of 8.2 nM, 19 nM, 56 nM, and 160 nM for BRAF V600E, BRAF, CRAF, and MEK1, respectively. Phase 1.

URMC-099 is an orally bioavailable, brain penetrant MLK inhibitor (IC50: 19/42/14/150 nM, for MLK1/MLK2/MLK3/DLK), and also inhibits LRRK2 activity (IC50: 11 nM).

U0126-EtOH (U0126 Ethanol) is a non-ATP competitive specific inhibitor of MEK1 2 (IC50: 0.07 0.06 μM).

1. Epiberberine may be caused drug interactions based on CYP2D6 enzyme. 2. Epiberberine has anti-adipogenic effect is mediated by downregulation of the Raf MEK1 ERK1 2 and AMPKα Akt pathways during 3T3-L1 adipocyte differentiation. 3. Epiberberine, as the brightest FSA emitter among the alkaloids, can also serve as an efficient conformation probe for HTG DNA and discriminate the DNA G-quadruplex from the RNA counterpart.

Morusinol is a flavonoid extracted from the root bark of Morus alba. Morusinol has antiplatelet and anticancer activities, inhibits arterial thrombosis in vivo, and exerts antitumor activity by inducing autophagy, G2 M cell cycle blockade, inhibiting cell invasion and migration, and targeting the Ras MEK ERK pathway.

Isorhamnetin (3-methylquercetin) is the methylated metabolite of quercetin. Quercetin is an important dietary flavonoid with in vitro antioxidant activity. Isorhamnetin prevents endothelial cell injuries from oxidized LDL via inhibition of lectin-like ox-LDL receptor-1 upregulation, interference of ox-LDL-mediated intracellular signaling pathway (p38MAPK activation, NF-kappaB nuclear translocation, eNOS expression) and the antioxidant activity of isorhamnetin. Isorhamnetin prevents endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II. Isorhamnetin appears to be a potent drug against esophageal cancer due to it's in vitro potential to not only inhibit proliferation but also induce apoptosis of Eca-109 cells.

5Z-7-Oxozeaenol (FR148083) is a potent, irreversible and selective inhibitor of transforming growth factor (TGF)-β-activated kinase 1 with IC50 of 8.1 nM for TAK1 and low activity against MEK1 with IC50 of 411 nM, it is also an inhibitor of VEGF-R2 with IC50 of 52 nM.

Pelitinib (EKB-569) (EKB-569) is an effective irreversible EGFR inhibitor (IC50: 38.5 nM).

Hederacolchiside A1 (Raddeanoside R13) shows anti-leishmanial activity, it exhibits a strong antiproliferative activity on all stages of development of the parasite by altering membrane integrity and potential. Hederacolchiside A1 shows antiproliferation activities in three cancer cell lines with the IC50 value of 2.4 uM, it exhibits a preferential cytotoxicity on a pigmented melanoma cell line. It suppresses proliferation of tumor cells by inducing apoptosis through modulating PI3K Akt mTOR signaling pathway.

CI-1040 (PD 184352) (PD184352) is an ATP non-competitive MEK1 2 inhibitor (IC50: 17 nM).

TAK-733 is an orally bioavailable small-molecule inhibitor of MEK1 and MEK2 (MEK1/2) with potential antineoplastic activity.

BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM.

Lidocaine hydrochloride (Lignocaine hydrochloride) is a local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.

BMS-536924 (BMS 536924) is an ATP-competitive IGF-1R IR inhibitor with IC50 of 100 nM 73 nM, modest activity for Mek, Fak, and Lck with very little activity for Akt1, MAPK1 2.

Lidocaine (Alphacaine) is an amide local anesthetic with anti-inflammatory properties in vitro and in vivo. It has this functions perhaps due to an attenuation of intracellular adhesion molecule-1 (ICAM-1), pro-inflammatory cytokines, and reduction of neutrophils influx.

Refametinib (RDEA119) (RDEA119, Bay 86-9766) is an effective, ATP non-competitive and specific inhibitor of MEK1 2 (IC50: 19 47 nM).

NST-628 is a pan-RAF-MEK molecular glue that prevents RAF from phosphorylating and activating MEK, inhibiting the RAF-MEK signaling complex.

BIX02188 is a selective and potent MEK5 inhibitor that inhibits MEK5-induced apoptosis in cells expressing the oncogenic mutant FLT3-ITD.

Anemarsaponin B has anti-inflammatory effect in LPS-treated RAW 264.7macrophages, the effect is associated with the inhibition of NF-κB transcriptional activity, possibly via the p38 MAP kinase pathway. Anemarsaponin B can inhibit PAF-induced rabbit platelet aggregation in vitro.

Trametinib (DMSO solvate) (GSK-1120212 (DMSO solvate)) is a highly potent and selective MEK inhibitor that specifically inhibits MEK1 2 (IC50: 2 nM).

Zapnometinib (ATR-002) is a MEK inhibitor.

BAY-6035 is an inhibitor of SET and MYND domain-containing protein 3 (SMYD3). BAY-6035 has more than 100-fold selectivity over other histone methyltransferases.

ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A B than MEK1, Src, Lck and has little effect against CDK1 2 4, Plk1, Chk1, etc.

trans-Zeatin ((E)-Zeatin) is the member of the plant growth hormone family known as cytokinins, which regulate cell division, development, and nutrient processing.

PD 198306 is a selective inhibitor of MAPK ERK-kinase (MEK) with antihyperalgesic effects. PD 198306 reduces the Streptozocin-induced increase in the level of active ERK1.

U0126, an effective and selective non-competitive inhibitor of MAP kinase, inhibits MEK-1 and MEK-2 with IC50 values of 0.07 and 0.06 μM respectively. U0126 inhibits autophagy and mitophagy.

RGB-286638 free base is a novel CDK inhibitor with IC50s of 1 nM/2 nM/3 nM/4 nM/5 nM for cyclin T1-CDK9/cyclin B1-CDK1/cyclin E-CDK2/cyclin D1-CDK4/cyclin E-CDK3/p35-CDK5 respectively; less potent against cyclin H-CDK7 and cyclin D3-CDK6.

GW284543 (UNC10225170) is a selective inhibitor of MEK5.

GDC-0623 (RG 7421) is a potent, ATP-uncompetitive MEK1 inhibitor with a Ki of 0.13 nM, currently in Phase 1.

EF24 (3,5-Bis[(2-fluorophenyl)Methylene]-4-piperidinone) treatment increases the levels of activated caspase 3 and 9, and decreases the phosphorylated forms of MEK1 and ERK. EF24 shows potent anti-tumor activity in oral squamous cell carcinoma (OSCC) via deactivation of the MAPK/ERK signaling pathway.

GW 284543 hydrochloride is a selective inhibitor of MEK5 .

BI-847325 is a selective dual inhibitor of MEK and aurora kinases (AK) with IC50 values of 4 and 15 nM for human MEK2 and AK-C, respectively.

Cobimetinib racemate (Cobimetinib (racemate)) (GDC-0973 racemate) is a selective inhibitor of MEK.Cobimetinib racemate is also known as a mitogen-activated protein kinase, is a key component of the RAS RAF MEK ERK pathway.

Bufarenogin (3beta,12beta,14-Trihydroxy-11-oxo-5beta-bufa-20,22-dienolide) is a bufadienolide isolated from parotoid gland secretions of the Cuban endemic toad Peltophryne fustiger. Bufarenogin shows anti-tumor activity.

TAK-285 is a novel dual HER2 and EGFR(HER1) inhibitor with IC50 of 17 nM and 23 nM, >10-fold selectivity for HER1 2 than HER4, less potent to MEK1 5, c-Met, Aurora B, Lck, CSK etc. Phase 1.

Kaempferol 3-neohesperidoside (Kaempferol 3-O-neohesperidoside), a flavonoid compound, exhibits an insulinomimetic effect on the rat soleus muscle.

PD184161 is a novel, orally-active MEK inhibitor. PD184161 inhibited MEK activity (IC50 = 10-100 nM) in a time- and concentration-dependent manner[1].

AZD8330 (ARRY-704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM. Phase 1.

APS-2-79 hydrochloride (APS-2-79 HCl) is a MAPK antagonist that modulating KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK.

SL327 is a selective inhibitor for MEK1/2 with IC50 of 0.18 μM/0.22 μM; able to transport through the blood-brain barrier.

Pimasertib (AS703026) is an orally bioavailable small-molecule inhibitor of MEK1 and MEK2 (MEK1/2) with potential antineoplastic activity.