MAPK信号通路

Nimbolide suppresses CDK4/CDK6 kinase activity. Nimbolide inhibits the NF-κB, Wnt, PI3K-Akt, MAPK, and JAK-STAT signaling pathways. Nimbolide causes apoptosis through the inactivation of NF-κB. Nimbolide is a triterpene derived from the leaves and flowers

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.

Chitosan oligosaccharide (COS) is an oligomer of β-(1→4)-linked D-glucosamine that activates AMPK while inhibiting inflammatory signaling pathways, including NF-κB and MAPK.

Amiodarone hydrochloride is an anti-anginal agent and a class III antiarrhythmic drug that inhibits potassium channels (including wild-type hERG channels and their tail currents, with an IC₅₀ of approximately 45 nM) as well as voltage-gated sodium channels. This leads to prolonged action potential duration in ventricular and atrial myocytes, resulting in reduced heart rate and vascular resistance. It activates ERK1/2 and p38 MAPK signaling pathways in fibroblasts, promoting cell proliferation and myofibroblast differentiation. Amiodarone hydrochloride is widely used in the study of supraventricular and ventricular arrhythmias and can also be used to establish pulmonary fibrosis animal models.

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.

Esculin (Aesculin) is a glucoside found in horse chestnuts.

Nisin Z has anti-inflammatory activity and reduces pro-inflammatory cytokine release by inhibiting activation of the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathways, attenuating lipopolysaccharide-induced mastitis through inhibition of the ERK1/2 and p38 mitogen-activated protein kinase signaling pathways.

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.

Maohuoside A promotes osteogenesis of rat mesenchymal stem cells via BMP and MAPK signaling pathways.

AMG-548 is a selective and orally active p38α MAPK inhibitor (Ki = 0.5 nM), with higher selectivity than p38β, p38γ, and p38δ, and can also inhibit the TNFα, CK1δ/ε, and Wnt signalling pathways.

Murrayafoline A is a natural carbazole alkaloid found primarily in plants of the genera Murraya and Glycosmis. Murrayafoline A directly targets Specific Protein 1 (Sp1), thereby inhibiting the NF-κB and MAPK signaling pathways. Murrayafoline A attenuates the Wnt/β-catenin pathway by promoting the degradation of intracellular β-catenin. Murrayafoline A induces G0/G1 phase arrest in platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells. Murrayafoline A enhances contractility and L-type calcium currents in rat ventricular myocytes by activating protein kinase C. Murrayafoline A inhibits LPS-induced neuroinflammation in vivo. Murrayafoline A can be used in research on inflammation, vascular complications, and colorectal cancer.

RV01 is a novel quinoline-substituted analogue of resveratrol that inhibits DNA damage, reduces ethanol-induced acetaldehyde dehydrogenase (ALDH2) mRNA expression, and has hydroxyl radical scavenging activity. rV01 reduces iNOS expression and has anti-neuroinflammatory effects. rV01 reduces tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion. RV01 reduced tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion, inhibited lps-induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, decreased toll-like receptor 4 (TLR4) protein expression, and inhibited lps-induced activation of mitogen-activated protein kinase (MAPK) and nuclear transcription factor-кB (NF-кB) signaling pathways.

BI-3406 is an orally active, highly potent and selective between KRAS and Son of Sevenless 1 (SOS1) interaction inhibitor(IC50 : 6 nM),with anticancer activity.

Balamapimod, also known as MKI-822, is a small-molecule Ras/Raf/MEK inhibitor that directly targets deregulated MAPK signaling cascades and is being actively explored to suppress aberrant protein kinase activity implicated in oncogenic transformation, inflammatory signaling, and pathological cell proliferation, with demonstrated therapeutic relevance for stroke, osteoporosis, rheumatoid arthritis, polycystic kidney disease, colonic polyps, and other inflammation-driven disorders through pathway-level inhibition.

SPP-86 is an effective and selective cell-permeable inhibitor of RET tyrosine kinase with an IC50 of 8 nM.

HRX-0233 is a small-molecule MAP2K4 inhibitor that induces strong tumor regression without apparent toxicity in KRASG12C-mutant non-small cell lung cancer models, prevents receptor tyrosine kinase feedback activation during sotorasib monotherapy. HRX-0233 achieves sustained MAPK pathway suppression, supporting its application in lung, colon, and AR-negative prostate cancer research.

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.

Antiproliferative agent-57 (compound M2) is a tumor angiogenesis inhibitor that suppresses VEGF secretion in SiHa cells under hypoxic conditions without inducing cytotoxicity (IC50=0.68 μM). It modulates the PI3K/AKT/mTOR and MAPK signaling pathways in tumor cells, thereby inhibiting the expression of HIF-1α and VEGF within tumor tissues.

Anti-osteoporosis agent-11 (compound 3k) is an anti-osteoporosis compound targeting osteoclasts. It exhibits its most prominent effect by inhibiting osteoclast differentiation, with an IC50 value of 0.36 μM. Additionally, Anti-osteoporosis agent-11 suppresses osteoclast formation, bone resorption, and the expression of osteoclast-specific genes by blocking the RANKL-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways.

Lambertellin, an effective antibiotic, acts as both a bactericide and fungicide. It exerts anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages by modulating the activation of MAPK and NF-κB signaling pathways.

RIPK2-IN-6 (Compound 15a) is an inhibitor of RIPK that specifically targets the phosphorylation of RIPK2, thereby suppressing the NF-κB and MAPK signaling pathways. It has demonstrated anti-inflammatory and anti-fibrotic activities in a mouse model of colitis induced by Dextran sodium sulfate.

MAPK-IN-3 (Compound 4a) is an antiproliferative agent demonstrating significant inhibitory effects on KYSE 30, HCT 116, and HGC 27 cell lines, with IC50 values of 0.57 μM, 3.27 μM, and 2.28 μM, respectively. This compound arrests the cell cycle via a p53-dependent mechanism and induces apoptosis through a p53-independent pathway. It reduces the expression of cell cycle-related proteins, such as Cyclin D1 and Cyclin B1, while increasing pro-apoptotic proteins like cleaved PARP, cleaved caspase-7, and cleaved caspase-9. MAPK-IN-3 also decreases anti-apoptotic proteins such as Bcl-2, elevates ROS levels in KYSE 30 cells, and enhances the expression of ROS-related MAPK pathway members, including p-ERK, p-p38, and p-JNK.

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.