MAPK

Gardenin A shows neurotrophic effects via activating MAPK ERK, PKC, and PKA. Gardenin A exhibits antidepressant, anticonvulsant and anxiolytic effects.

SKLB-163 acts by downregulating RhoGDI, activating JNK-1 signaling pathway and caspase-3, and reducing phosphorylated Akt and p44 42 MAPK.

Darizmetinib (HRX215, HRX-0215) is an MKK4 inhibitor. Inhibition of MKK4 leads to enhancement of the MKK7 and JNK1 signaling pathways, thereby activating the transcription factors ATF2 and ELK1, promoting cell proliferation and liver regeneration.

GNE-1858 is an ATP-competitive hematopoietic progenitor kinase-1 (HPK1) inhibitor (IC50s of 1.9 nM, 1.9 nM, and 4.5 nM for wild-type and the active mimetic mutants HPK1-TSEE and HPK1-SA).

Beta-Tocopherol has effects on human erythroleukemia cell (HEL) adhesion induced by phorbol 12-myristate 13-acetate (PMA).

Vemurafenib (RG7204) is a B-RAF inhibitor that inhibits RAFV600E and c-RAF-1 (IC50=31 48 nM) selectively and potently. Vemurafenib exhibits antitumor activity and is used for the treatment of BRAF V600E mutation-positive melanoma.

DMX-5804 is a potent, selective MAP4K4 inhibitor, with an IC50 of 3 nM.DMX-5804 enhances cardiomyocyte survival, and reduces ischemia-reperfusion injury in mice.

HS-276 is a highly selective, orally active inhibitor of TAK1 (Ki: 2.5 nM). HS-276 significantly inhibits TAK1 (IC50: 8.25 nM), CLK2 (IC50: 29 nM), GCK (IC50: 22 nM), ULK2 (IC50: 63 nM), MAP4K5 (IC50. HS-276 can be used to study rheumatoid arthritis (RA).

Takinib (EDHS-206) is a specific and effective TAK1 inhibitor(IC50= 9.5 nM).

1. Norisoboldine ((+)-Laurelliptine) might be a potential therapeutic agent for rheumatoid arthritis, and it functions through protecting joint destruction as well as regulating the abnormal immune responses. 2. Norisoboldine inhibits the macrophage activation and the resultant production of pro-inflammatory cytokines via down-regulating the activation of MAPKs signaling pathways rather than NF-κB.

CC-99677 (Gamcemetinib) is a selectively targeted covalent MAPKAPK2 (MK2) inhibitor for autoimmune diseases that translates biochemical potency into cellular potency as demonstrated by potent inhibition of heat shock protein 27 (HSP1) phosphorylation in LPS-activated monocyte THP-27 cells via a nucleophilic aromatic substitution (SNAr) mechanism.CC-99677 in Rat experiments demonstrated potency in both biochemical (IC 50 =156.3 nM) and cellular assays (EC 50 =89 nM).

MBM-55 is an effective inhibitor of NIMA related kinase 2 (NEK2) with an IC50 of 1 nM. MBM-55 effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis.

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.

Selonsertib (GS-4997) is an orally bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with potential anti-inflammatory, antineoplastic and anti-fibrotic activities.

GNE-3511 is a potent and selective dual leucine zipper kinase inhibitors.

PF-06260933 is a highly selective small-molecule MAP4K4 inhibitor with IC50s of 3.7 and 160 nM for kinase and cell, respectively.

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

Rehmannioside A, a cyclic enol ether terpene glycoside extracted from the traditional Chinese medicine Dihuang, possesses neuroprotective activity and acts by inhibiting NF-κB and MAPK signaling pathways.

A-443654, a pan-Akt inhibitor, exhibits equal potency against Akt1, Akt2, and Akt3 within cells (Ki=160 pM).

NG25 is a potent dual inhibitor of TAK1 and MAP4K2, with IC50s of 149 nM and 21.7 nM, respectively.

NCB-0846 is an orally active TNIK inhibitor (IC50: 21 nM).

Pan-RAS-IN-1 is an inhibitor of pan-Ras. It disrupts the interaction of Ras proteins and their effectors.

Scandoside, a cyclic enolide that can be isolated from Haemophilus difficile, exhibits anti-inflammatory activity, inhibits the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 messenger RNA (mRNA), and inhibits the nuclear transcription factor, kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitor phosphorylation.

Semapimod tetrahydrochloride (CPSI-2364 tetrahydrochloride) is a synthetic ornithine mitogen-activated protein kinase blocker and pro-inflammatory cytokine production inhibitor that interferes with macrophage and microglia function. Sematimod tetrahydrochloride inhibits TLR4 signaling, TNF-α, IL-1β, and IL-6, and is used in the study of Crohn's disease and other inflammatory conditions.

3',4',7-Trihydroxyisoflavone is a soy isoflavone soy glycoside derivative and Cot (Tpl2 MAP3K8) and MKK4 inhibitor with anticancer, antiangiogenic and free radical scavenging properties.3',4',7-Trihydroxyisoflavone enhances memory effects through modulation of cholinergic function and BDNF signaling pathway in mice.3',4',7-Trihydroxyisoflavone can improve skin barrier function impaired by endogenous or exogenous glucocorticoids and can be used in the study of atopic dermatitis. 3',4',7-Trihydroxyisoflavone enhances memory effects by modulating cholinergic function and BDNF signaling pathway in mice. It can improve the skin barrier function impaired by endogenous or exogenous glucocorticoids, and can be used in the study of atopic dermatitis.

NMS-P715 is a selective and ATP-competitive MPS1 inhibitor(IC50 of 182 nM).

MBM-55S is an effective inhibitor of Nek2 with an IC50 of 1 nM. MBM-55S indecus cell cycle arrest and apoptosis thereby inhibiting the proliferation of cancer cells. MBM-55S shows antitumor activities.

GNE-495 is a potent and specific inhibitor of MAP4K4 with an IC50 of 3.7 nM.

TAK1-IN-3 is a novel ATP-competitive TAK1 inhibitor for the study of cancer.

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.

SM1-71 is a potent multi-targeted acrylamide-modified TAK1 inhibitor that inhibits MKNK2, MAP2K1 2 3 4 6 7, GAK, AAK1, BMP2K, MAP3K7, MAPKAPK5, GSK3A B, MAPK1 3, SRC, YES1, FGFR1, ZAK (MLTK), MAP3K1, LIMK1 and RSK2.SM1-71 can be used as a kinase probe with anticancer activity and inhibits the proliferation of various cancer cell lines.

ASK1-IN-2 is a potent, orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with an IC50 of 32.8 nM. It has potential therapeutic applications for ulcerative colitis[1].

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)

MAP4K4-IN-3 (Compound 17), a serine threonine protein kinase, may be a viable target for antidiabetic agents.

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

Nomilin is naturally occurring triterpenoids, have immunomodulatory activity.

(R)-STU104 is a novel TAK1-MKK3 protein-protein interaction (PPI) inhibitor that inhibits TNF-α and suppresses the TAK1 MKK3 p38 MnK1 MK2 elF4E signalling pathway by binding to MKK3 and disrupting TAK1 phosphorylation of MKK3. (R)-STU104 is a candidate compound for the treatment of ulcerative colitis.

GS-444217 is a selective ATP-competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1, IC50: 2.87 nM).

Eudesmin shows antiinflammatory, neuritogenic, anticonvulsant and sedative effects, the mechanism of eudesmin may be related to up-regulation of GABAA and GAD65 expressions, and anti-apoptosis of neuron the in brain.50 microM (+)-eudesmin can induce neurite outgrowth and enhance nerve growth factor (NGF)-mediated neurite outgrowth from PC12 cells by stimulating up-stream MAPK, PKC and PKA pathways.

TAO Kinase inhibitor 1 delays mitosis and induces mitotic cell death. TAO Kinase inhibitor 1 is a selective and ATP-competitive thousand-and-one amino acid kinases inhibitor (IC50s: 11 to 15 nM for TAOK1 and 2, respectively).

NF-κB MAPK-IN-1 is a potent dual inhibitor of the NF-κB and MAPK pathways with potential anti-inflammatory activity, inhibition of NO production, and inhibition of LPS-induced activation of iNOS, COX-2, ERΚ and P38. NF-κB MAPK-IN-1 is used for the prevention and treatment of rheumatoid arthritis (RA).

HS-243 is an inhibitor of IRAK-4 and IRAK-1 with IC50s of 20 and 24 nM. HS-243 shows anti-inflammatory and anticancer activity.

Bisabolangelone has anti-tumor, anti-inflammatory, anti-microbial, and antioxidant activities, it inhibits dendritic cell functions by blocking MAPK and NF-κB signaling.

TC ASK 10 is a potent, selective and orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1)(IC50 of 14 nM).

Cot inhibitor-2 is a cot (Tpl2 MAP3K8) inhibitor (IC50: 1.6 nM) with potency, selectivity and oral activity. cot inhibitor-2 inhibits LPS-stimulated TNF-α production in human whole blood with an IC50 of 0.3 μM.

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

ZINC05007751 is an effective inhibitor of NIMA-related kinase NEK6 (IC50 = 3.4 μM). ZINC05007751 is very selective against NEK1 and NEK6 with no significant activity observed against NEK2, NEK7, and NEK9.

HPK1-IN-4 is an HPK1 (MAPK41) inhibitor with an IC 50 of 0.061 nM. HPK1-IN-4 is often used as a preclinical immunotherapy tool compound.