mapk-2

p38 MAPK-IN-2 is a potent inhibitor of p38 kinase.

MAPK-IN-2 (compound 3h) is an efficacious MAPK inhibitor with antineoplastic properties that significantly hinders proliferation across various cancer cell lines. It demonstrates robust suppression of the MAPK pathway (EGFR WT IC50 = 281 nM, c-MET IC50 = 205 nM, B-RAF WT IC50 = 112 nM, CDK4 6 IC50 = 95 and 184 nM, respectively) and exhibits pronounced activity against mutated forms of EGFR and B-RAF (EGFR T790M IC50 = 69 nM and B-RAF V600E IC50 = 83 nM) [1].

p44/42 MAPK (Erk1/2) (137F5) Rabbit mAb #4695R is a useful organic compound for research related to life sciences and the catalog number is T64587.

Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (20G11) Rabbit mAb #4376R is a useful organic compound for research related to life sciences and the catalog number is T64608.

Butein (2’,3,4,4’-tetrahydroxy Chalcone), a plant polyphenol, is isolated from Rhus verniciflua. It can inhibit the activation of protein tyrosine kinase, NF-κB and STAT3, and also can inhibit EGFR.

LXH254 is a potent C-Raf and B-Raf inhibitor.

Afatinib Dimaleate (BIBW 2992MA2) is an orally bioavailable anilino-quinazoline derivative and inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with antineoplastic activity.

Amiodarone hydrochloride (Amiodarone HCl) is an antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.

3'-Hydroxypterostilbene (3'-HPT), a natural pterostilbene analogue, effectively inhibits the growth of human colon cancer cells with IC50s of 9.0, 40.2, and 70.9 μM for COLO 205, HCT-116, and HT-29 cells, respectively, by inducing apoptosis and autophagy. 3'-Hydroxypterostilbene inhibits the p38MAPK , and PI3K/Akt/mTOR/p70S6K pathways and activates the ERK1/2, JNK1/2 MAPK pathways[1].

Fumaric acid (2-Butenedioic acid) attenuates the eotaxin-1 expression in TNF-α-stimulated fibroblasts by suppressing p38 MAPK-dependent NF-κB signaling. Fumaric acid has recently been identified as an oncometabolite or an endogenous, cancer-causing metabolite. High levels of this organic acid can be found in tumors or biofluids surrounding tumors. Its oncogenic action appears due to its ability to inhibit prolyl hydroxylase-containing enzymes.

Afatinib (BIBW 2992) is an irreversible inhibitor of the EGFR family (EGFR-wt, EGFR-L858R, EGFR-L858R T790M, and HER2) with IC50s of 0.5 nM, 0.4 nM, 10 nM, and 14 nM, respectively.

GS87 is a highly specific inhibitor of GSK3 (glycogen synthase kinase 3) that induces extensive differentiation of AML cells.

5-OxoETE is a polyunsaturated keto acid formed by the oxidation of 5-HETE in human neutrophils by a specific dehydrogenase.[1] It stimulates cytosolic calcium levels in neutrophils with an EC50 value of 2 nM.[2] 5-OxoETE selectively stimulates the migration and degranulation of eosinophils and activates the MAPK pathway in stimulated neutrophils via a specific G protein-coupled receptor.[3],[4],[5],[6]

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.

Theaflavin 3,3'-digallate (8-Gingerol) , a major polyphenol found in black tea, is an inducer of oxidative stress which has anti-inflammatory and cancer chemopreventive actions, it reduces tumor angiogenesis by downregulating HIF-1αand VEGF.

Rineterkib (ERK-IN-1) is an inhibitor of RAF and ERK1/2 activating mutations in the MAPK pathway.

1. Isoquercetin (3-Glucosylquercetin) is a potential stimulator of bone mineralization used for prophylaxis of osteoporotic disorders. 2. Isoquercetin may be as a potential therapeutic agent against neurodegeneration in Parkinson's disease. 3. Isoquercetin is an inhibitor of Wnt/β-catenin and may be as a potential novel anti-tumoral agent, such as against human pancreati,liver cancer related to opioid receptors and to the activation of the mitogen-activated protein kinase (MAPK) signalling pathway. .

Lawsone methyl ether (2-Methoxy-1,4-naphthoquinone) induces apoptosis in A549 cells independently of cell cycle arrest, mediated by JNK and p38 MAPK signaling pathways. These pathways are activated due to oxidative DNA damage from increased ROS generation in MNQ-treated A549 cells.

Calycosin (Cyclosin) acts as a selective estrogen receptor modulator. Calycosin induces apoptosis in human ovarian cancer SKOV3 cells by activating caspases and Bcl-2 family proteins. Calycosin suppresses breast cancer cell growth via ERβ-dependent regulation of IGF-1R, p38 MAPK and PI3K/Akt pathways. Calycosin has antineoplastic effects against osteosarcoma through inducing apoptosis showing in vitro and in vivo investigations. Calycosin was shown to induce angiogenesis in human umbilical vein endothelial cell cultures (HUVEC) in vitro. Calycosin may be an effective skin-lightening agent that regulates the expression of melanogenic enzymes. Calycosin exhibited tyrosinase inhibitory activity with an IC(50) value of 38.4 microM.

Neochlorogenic acid (trans-5-O-Caffeoylquinic acid) is an antioxidant compound used in the treatment of oxidative stress and related afflictions.

Rosmanol has antioxidant activity, it can activate the antioxidant response element. Rosmanol has biphasic modulation of GABAA receptors, demonstrates CNS activity in mouse models of antinociception, antidepressant and anxiolysis. Rosmanol potently induce

1. Flavokawain B (Flavokavain B) has potent anti-inflammatory activity, can significantly inhibit production of NO and PGE2 in LPS-induced RAW 264.7 cells. 2. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathways. 3. Flavokawain B induces apoptosis, has the potential usefulness of FKB for prevention and treatment of hormone-refractory prostate cancer in an adjuvant setting. 4. Flavokawain B acts through ROS generation and GADD153 up-regulation to regulate the expression of Bcl-2 family members, thereby inducing mitochondrial dysfunction and apoptosis in HCT116 cells.

1. Cornuside (Comuside) has immunomodulatory activity . 2. Cornuside suppresses expression levels of cytokine-induced proinflammatory and adhesion molecules in the human endothelial cells. 3. Cornuside can treat myocardial I/R and protect the liver from CCl4-induced acute hepatotoxicity, by reducing oxidative stress and suppressing inflammatory responses. 4. Cornuside has anti-inflammatory activity by downregulations of iNOS and COX-2 due to NF-κB inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7 cells. 5. Cornuside has protective potential against cerebral ischemic injury, may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvements in mitochondrial energy metabolism and antioxidant properties.

Losmapimod (GSK-AHAB) (GW856553X; SB856553; GSK-AHAB) is a specific, potent, and orally active p38 MAPK inhibitor (pKi: 8.1/7.6 for p38α/β).

Adezmapimod (SB 203580) is a selective, ATP-competitive p38 MAPK inhibitor (IC50=0.3-0.5 μM) that activates autophagy and mitochondrial autophagy, with more than 100-fold higher selectivity over PKB, LCK, and GSK-3β.

1. Vitexin has antinociceptive and antispasmodic activities. 2. Vitexin exhibits a prominent first-pass effect. 3. Vitexin has antioxidant, antimyeloperoxidase, and α-glucosidase inhibitory activities. 4. Vitexin can either inhibit or induce activities of

1. 6-Shogaol (6-Shogaol) has antipyretic and analgesic effects in addition to inhibitory effect on lipoxygenase activity. 2. 6-shogaol has anti-inflammatory property, reduces the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats. 3. 6-Shogaol inhibits the growth of human cancer cells and induces apoptosis in COLO 25 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). 4. 6-Shogaol effectively inhibit invasion and metastasis of hepatocellular carcinoma through diverse molecular mechanisms, including inhibition of the MAPK and PI3k/Akt pathways and NF-κB and STAT3 activities to suppress expression of MMP-2/-9 and uPA and block angiogenesis, could further regulate urokinase-type plasminogen activity.

1. Schisandrol B (Besigomsin) may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. 2. Schisandrol B has anti-inflammatory property, potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. 3. Schisandrol B induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. 4. Schisandrol B significantly inhibits cell proliferation in a dose-dependent manner, due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation.

Momordin Ic (Momordin 1c) might represent a potential anticancer activity, by inducing apoptosis through oxidative stress-regulated mitochondrial dysfunction involving the MAPK and PI3K-mediated iNOS and HO-1 pathways. Also, Momordin Ic accelerates gastrointestinal transit partially by stimulating synthesis of 5-HT to act through 5-HT(2), which, in turn, increases synthesis of prostaglandins.

MK2-IN-1 hydrochloride (MK 25) is a highly selective, non-ATP competitive inhibitor of p38/mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2 or MK2, IC50: 0.11 μM) [1].

1. Decursin (Decursinol angelate) is able to attenuate kainic acid-induced seizures and could have potential as an antiepileptic drug. 2. Decursin exhibits hepatoprotective effects , potentially by inhibiting the TGF-β1 induced NOX activation and Smad signaling. 3. Decursin has anti-cancer activity , mediated suppression of the PKCα, MAPK and NF-κB pathways in MCF-7 cells. 4. Decursin exhibits cytotoxicity against various human cancer cells and to possess anti-amnesic activity in vivo through the inhibition of AChE activity.

N-tert-butyl-α-Phenylnitrone ((Z)-N-benzylidene-2-Methylpropan-2-aMine oxide) inhibits COX2 catalytic activity. N-tert-butyl-α-Phenylnitrone((Z)-N-benzylidene-2-Methylpropan-2-aMine oxide) possesses potent reactive oxygen species scavenging, anti-inflammatory, neuroprotective, anti-aging, and anti-diabetic activities, and can penetrate the blood-brain barrier.

CAY10404 (3-(4-METHYLSULPHONYLPHENYL)-4-PHENYL-5-T) is a potent and highly selective inhibitor of COX-2 and COX-1. It is also a potent inhibitor of PKB Akt and MAPK signalling pathways and induces apoptosis in NSC-LC cells, with analgesic, anti-inflammatory and anti-cancer activities.

Olodanrigan (EMA401), a highly selective AT2R antagonist, inhibition of augmented AngII/AT2R induced p38 and p42/p44 MAPK activation, and hence inhibition of DRG neuron hyperexcitability and sprouting of DRG neurons. EMA401 blocks p38, p42/p44 mitogen-activated protein kinase (MAPK) activation, neurite outgrowth in adult rat DRG neurons, and sensitization of adult rat and human DRG neurons induced by AngII. It inhibits capsaicin responses in cultured hDRG neurons.

L-quebrachitol is a natural product.L-quebrachitol may promote osteoblastogenesis by triggering the BMP-2-response as well as the Runx2, MAPK, and Wnt β-catenin signaling pathway.

1. Nitidine chloride has inhibitory effects on various tumors, such as renal cancer , breast cancer. 2. Nitidine chloride inhibits the proliferation of SMMC-7721 cells in vitro in a time- and dose-dependent manner and identifies efficacy in vivo in a mouse model of HCC.

Pexmetinib (ARRY-614) (ARRY-614) is a potent, orally bioavailable, dual p38 MAPK Tie-2 inhibitor with IC50 of 4 nM 18 nM in a HEK-293 cell line. Phase 1.

SD 0006 (SD-06) is a MAPK p38 alpha inhibitor with an IC50 of 110 nM, indicated for the treatment of arthritis.

Toddaculine may be beneficial for the prevention and treatment of osteoporosis, it can not only inhibit the differentiation of osteoclasts via activation of the NF-κB, ERK 1 2, and p38 MAPK signaling pathways, but can induce differentiation and mineralization of osteoblasts by regulating differentiation factors. Toddaculine also may serve as a pharmacological prototype for the development of novel anti-leukemic agents, it displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells.

Sertaconazole is a broad-spectrum antifungal.

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.

PF-3644022 is an effective, selective, and ATP-competitive MAPKAPK2 (MK2) inhibitor (IC50: 5.2 nM and a Ki of 3 nM). PF-3644022 potently inhibits TNFα production and has an anti-inflammatory effect. PF-3644022 also inhibits MK3 and p38 regulated activated

1. 8-Gingerol has antioxidant activity. 2. 8-Gingerol has antimycobacterial activity. 3. 8-Gingerol could be used as an effective skin-whitening agent. 4. 8-Gingerol shows antipyretic and anti-inflammation characteristics. 5. 8-Gingerol seems to be effect

MK2-IN-3 (MK2 Inhibitor III) is a potent, cell-permeable inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) and can be used for the treatment of rheumatoid arthritis

Paris saponin VII (Dioscini) shows inhibitory effects on cell proliferation.

CMPD1 is a non-ATP-competitive p38 MAPK-mediated MK2 phosphorylation inhibitor(apparent Ki (Kiapp): 330 nM).

HG-10-102-01 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2, IC50 of 20.3 nM).

MK2-IN-3 hydrate (MK-2 Inhibitor III) is an orally active, selective, and ATP-competitive inhibitor of MAPKAP-K2 (MK-2) (IC50 of 0.85 nM)

AS1940477 is p38 MAPK inhibitor. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms. In human peripheral blood mononuclear cells, AS1940477 inhibited lipopolysaccharide (LPS)- or phytohemagglutinin A (PHA)-induced production of proinflammatory cytokines, including TNFα, IL-1β, and IL-6 at low concentrations (LPS/TNFα, IC(50)=0.45n M; PHA/TNFα, IC(50)=0.40 nM). In addition, equivalent concentrations of AS1940477 that inhibited cytokine production also inhibited TNFα- and IL-1 β-induced production of IL-6, PGE(2), and MMP-3 in human synovial stromal cells. AS1940477 was also found to potently inhibit TNF production in whole blood (IC(50)=12 nM) and effectively inhibited TNFα production induced by systemically administered LPS in rats at less than 0.1mg/kg (ED(50)=0.053 mg/kg) with an anti-inflammatory effect lasting for 20h after oral administration. Overall, this stu......

Jatrorrhizine chloride (Neprotine chloride) is a potent and orally active uptake-2 transporter inhibitor. It exhibits a critical neuroprotective role in H2O2-induced apoptosis via inhibition of the MAPK pathway in HT22 hippocampal neurons.