mapk signaling pathway

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

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.

Scutellarin (Scutellarein-7-glucuronide), an active flavone isolated from Scutellaria baicalensis, can inhibit RANKL-mediated MAPK and NF-κB signaling pathway in osteoclasts, and down-regulate the STAT3 Girdin Akt signaling in HCC cells.

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

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

Diazepinomicin is a secondary metabolite produced by Micromonospora sp. It inhibits the EGF-induced Ras-ERK MAPK signaling pathway and induces apoptosis. Diazepinomicin also is an anti-tumor agent for K-Ras mutant models.

HRX-0233 is a small molecule inhibitor targeting MAP2K4. In vivo, HRX-0233 effectively reduces tumors in H358 KRASG12C mutant non-small cell lung cancer (NSCLC) without significant toxicity. This compound also prevents feedback activation of receptor tyrosine kinases (RTKs) when used as a monotherapy with the KRAS inhibitor Sotorasib, leading to more sustained and comprehensive inhibition of the MAPK signaling pathway. HRX-0233 holds potential for research in AR-negative prostate cancer, lung cancer, and colon cancer.

SKLB646 is an orally active multitarget kinase inhibitor that exhibits potent suppression of several kinases. It demonstrates significant inhibitory effects on SRC and VEGFR2, with IC50 values of 0.002 μmol L and 0.012 μmol L, respectively. Additionally, SKLB646 shows notable inhibition of B-Raf and C-Raf, with IC50 values of 0.022 μmol L and 0.019 μmol L, respectively. The compound inhibits the activation of the SRC signaling pathway and blocks the MAPK signaling pathway by inhibiting Raf kinases. Furthermore, SKLB646 inhibits the proliferation, migration, and invasion of human umbilical vein endothelial cells (HUVEC), thereby suppressing tumor-induced angiogenesis. SKLB646 also displays significant anti-proliferative and anti-survival effects on triple-negative breast cancer (TNBC) cell lines.

TB22 is a non-nucleoside inhibitor of DOT1LR231Q with anticancer activity. It inhibits the malignant phenotype of lung cancer cells harboring the R231Q mutation via the MAPK ERK signaling pathway, making it useful for lung cancer research.

SHP2-IN-33 (Compound D13) is an allosteric inhibitor of SHP2, exhibiting an IC50 of 1.2 μM against SHP2. It demonstrates an antiproliferative IC50 of 38 μM in Huh7 cells by blocking the G0 G1 cell cycle, inducing apoptosis (Apoptosis), and inhibiting the MAPK signaling pathway. In a Huh7 xenograft mouse model, SHP2-IN-33 shows significant antitumor activity and favorable pharmacokinetic properties, including 54% oral bioavailability and a half-life of 10.57 hours. SHP2-IN-33 holds potential for research involving SHP2-associated tumor diseases.

PROTAC BTK Degrader-13 (Compound 25) is a targeted BTK PROTAC degrader with a DC50 of 0.27 μM. It inhibits BTK activity with an IC50 of 0.44 μM and suppresses IL-2-induced T cell kinase (ITK) with an IC50 of 2.16 μM. This compound also inhibits the p38 MAPK signaling pathway, thereby blocking the activation of the BCR (B cell receptor) signaling pathway. [Pink: ligand for target protein BTK ligand 15; Black: linker; Blue: ligand for E3 ligase cereblon]

KRAS inhibitor-27 (Compound 15h) is a KRAS inhibitor that effectively targets KRAS G12D G12V mutated cells (AsPC-1 and SW620) and wild-type KRAS cells (HT-29), with IC50 values of 378 nM, 0.6 nM, and 3230 nM, respectively. It reduces ERK phosphorylation, with IC50 values of 0.6 nM and 1 nM in AsPC-1 and SW620 cells, respectively, and decreases DUSP4 expression, thereby inhibiting the MAPK signaling pathway.

CB1R antagonist 2 (Compound 11g) functions as an antagonist of the cannabinoid receptor 1 (CB1R), inhibiting the MAPK NF-κB signaling pathway and exhibiting anti-inflammatory properties. In RAW264.7 cells, it suppresses LPS-induced expression of IL-6, IL-1β, and TNF-α. In murine models, it improves OVA-induced allergic rhinitis.

PROTAC K-Ras Degrader-4 (Compound 4) is a proteolysis-targeting chimera (PROTAC) molecule designed to selectively degrade oncogenic mutants of K-Ras, effectively degrading KRASG12D in the GP5d cell line and KRASG12V in SW620 cells with DC50 of 1 nM and 13 nM, respectively; it concomitantly inhibits the downstream MAPK signaling pathway and represents a novel therapeutic strategy for cancer research targeting previously undruggable Ras mutations.

Anti-STEAP2 Antibody (AZD0516 antibody) is a selective inhibitor of the prostate-specific six transmembrane epithelial antigen 2 (STEAP2). It inhibits the proliferation, migration, and invasion of prostate cancer cells by blocking the STEAP2-mediated ERK/MAPK signaling pathway. Anti-STEAP2 Antibody shows potential for prostate cancer research.

WNK-IN-B is an inhibitor of Wnk signalling. WNK-IN-B is a cell-permeable diaminoacridine derivative that targets the CCT domain of SPAK and OSR1 via reversible binding. WNK-IN-B selectively suppress hypotonic shock-induced WNK signaling pathway activation

β-Elemonic Acid (3-Oxotirucallenoic Acid) exhibits anti-inflammatory effects. Beta-Elemonic acid inhibits proliferation by inducing hypoploid cells and cell apoptosis, the anticancer effects of beta-Elemonic acid are related to the MAPK signaling pathway, ROS activation and glutathione depletion in human A549 lung cancer cells. Beta-Elemonic acid exhibits prolyl endopeptidase inhibitory activities.

Apelin-12 acetate possesses a high affinity to orphan receptor APJ receptor. Apelin-12 acetate inhibits the JNK and p38 MAPK signaling pathway of the apoptosis-related MAPKs family, thus offering protection to neurons.

4'-Methoxyresveratrol (4'-O-Methylresveratrol) is a natural product from the roots of *Rheum palmatum* L., with significant hypoglycemic, anti-inflammatory, and antioxidant effects. 4'-Methoxyresveratrol alleviates AGE-induced inflammation by suppressing RAGE-mediated MAPK NF-κB signaling pathway and NLRP3 inflammasome activation.

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.

MAPK-IN-1 (Compound 2) is an inhibitor of the MAPK signaling pathway with anti-neuroinflammatory and neuroprotective activities, suitable for Alzheimer's disease research. It inhibits AChE with an IC50 of 23.84 μM [1].

Anti-inflammatory agent 21 (compound 9o) is a low cytotoxic, orally active anti-inflammatory agent that targets NO (IC50: 0.76 μM). It accumulates ROS and inhibits the NF-κB MAPK signaling pathway to exert anti-inflammatory effects, showing beneficial effects on cartilage destruction and inflammatory cell infiltration in a rat model of arthritis.

Exarafenib (RAF KIN_2787) is a potent, orally available pan-RAF inhibitor with antitumor activity that acts by inhibiting downstream MAPK pathway signaling. It is used in cancer research.

RO4927350 is a potent and highly selective non-ATP-competitive MEK1 2 inhibitor. RO4927350 selectively blocks the MAPK pathway signaling both in vitro and in vivo, which results in significant antitumor efficacy in a broad spectrum of tumor models. RO4927350 inhibits not only ERK1 2 but also MEK1 2 phosphorylation. In cancer cells, high basal levels of phospho-MEK1 2 rather than phospho-ERK1 2 seem to correlate with greater sensitivity to RO4927350. Furthermore, RO4927350 prevents a feedback increase in MEK phosphorylation, which has been observed with other MEK inhibitors. RO4927350 represents a novel therapeutic modality in cancers with aberrant MAPK pathway activation.