JNK Inhibitor

Epimedin B (Epmedin B) is a flavonoid active component found in Epimedium, with oral activity, and exhibits anti-osteoporotic and neuroprotective effects. Epimedin B inhibits RANKL-induced osteoclast differentiation, F-actin ring formation, and mature osteoclast bone resorption, inhibits the phosphorylation of JNK, p38 MAPK, PI3K, and AKT, activates the AMPK-Nrf2 antioxidant pathway, and reduces cellular and mitochondrial ROS. Epimedin B acts on ESR1 and exerts its effects via GPER. Epimedin B alleviates bone loss and improves bone microstructure in vivo, and in Parkinson's models protects dopaminergic neurons and maintains striatal dopamine levels through anti-apoptotic and anti-endoplasmic reticulum stress effects. Epimedin B can be used for research related to osteoporosis, diabetic osteoporosis, and Parkinson's disease.

Platycodin D3 is a triterpenoid saponin that can be found in Platycodon grandiflorum. Platycodin D3 exhibits multiple activities including anti-inflammation, regulation of airway mucus secretion, improvement of asthmatic airway inflammation and remodeling, and inhibition of hepatitis C virus (HCV) replication. The IC₅₀ value of Platycodin D3 against HCV NS5B RNA-dependent RNA polymerase is 8 μg/mL. Platycodin D3 can be used in studies related to asthma, hepatitis C virus infection and inflammatory diseases.

5-O-Methylvisammioside (4'-O-β-D-Glucosyl-5-O-methylvisamminol) is an orally active natural chromone glycoside and multiple biological activities. 5-O-Methylvisammioside inhibits ferroptosis by activating the Nrf2/HO-1 signaling axis. 5-O-Methylvisammioside alleviates intestinal barrier damage by inhibiting the ROS/NF-κB/NLRP3 pathway. 5-O-Methylvisammioside exerts a protective effect against acute liver injury by reducing ALT/AST, decreasing inflammatory infiltration, and inhibiting IκB-α phosphorylation and NF-κB nuclear translocation. 5-O-Methylvisammioside blocks the HMGB1/RAGE/MEK/ERK signaling axis to exert anti-tumor and anti-angiogenic effects. 5-O-Methylvisammioside improves depression-like behaviors by inhibiting Src kinase and the NF-κB pathway.

Geranial is an aromatic compound. It can be isolated from the fruits of Litsea cubeba Lour and the rhizomes of ginger (Zingiber officinale). Geranial inhibits LPS-induced phosphorylation of ERK1/2, JNK1/3 and IκB in macrophages. It suppresses the secretion of IL-1β, TNF-α and IL-6, as well as the expression of pro-IL-1β, iNOS and COX-2. Geranial increases ROS. It can be used in the research of inflammatory diseases.

Oxypeucedanin is a furanocoumarin derivative found in Angelica dahurica. Oxypeucedanin is an orally active PI3K/AKT/NF-κB, MAPK, and ROS inhibitor. Oxypeucedanin induces cell cycle arrest and apoptosis. Oxypeucedanin inhibits hKv1.5 channel currents (IC₅₀: 76 nM). Oxypeucedanin exhibits anticancer, anti-inflammatory, antioxidant and antiarrhythmic activities.

Seratrodast (AA 2414), an orally active antiasthmatic agent, is a thromboxane A2 receptor (TP) antagonist and ferroptosis inhibitor. Seratrodast reduces lipid ROS production, modulates the systemic xc-/GSH/GPX4 axis, and inhibits JNK phosphorylation and p53 expression. Seratrodast exhibits anti-asthmatic and anti-epileptic activity.

Keracyanin chloride inhibits NF-κB/FAK/MAPK signaling pathway. Keracyanin chloride exhibits antioxidant, anti-inflammatory and hypoglycemic effects, and is orally active.

Oleuropein Aglycone (3,4-DHPEA-EA) is a secoiridoid that exerts antioxidant, anti-inflammatory, and anti-apoptotic effects by promoting ERK/AMPK/eNOS phosphorylation and inhibiting JNK/p38 MAPK and inflammation-related signaling pathways. Oleuropein Aglycone is used in research on acute kidney injury induced by ischemia-reperfusion injury, pleurisy, osteoporosis, Alzheimer's disease, neurodegenerative diseases, and triple-negative breast cancer.

Tauroursodeoxycholate dehydrate is an orally active taurine conjugate of Ursodeoxycholic acid (HY-13771). Tauroursodeoxycholate dehydrate inhibits caspase-3/7, Apoptosis, IRE1α/TRAF2/NF-κB, prevents JNK phosphorylation, inhibits ROS generation, and activates Akt signaling. Tauroursodeoxycholate dehydrate prevents cataract formation, reduces renal tubular damage in type 2 diabetic mice, reduces I/R injury in liver, and inhibits intestinal inflammation and barrier disruption in nonalcoholic fatty liver disease.

Oroxylin A-7-O-glucuronide (oroxyloside) is an orally active flavonoid glucuronide and metabolite of Oroxylin A (HY-N0560). Oroxylin A-7-O-glucuronide can be extracted from the dried root of Scutellaria baicalensis. Oroxylin A-7-O-glucuronide exhibits prolyl oligopeptidase inhibitory activity. Oroxylin A-7-O-glucuronide inhibits the JNK pathway, upregulates PPARγ, and inhibits NF-κB p65 nuclear translocation. Oroxylin A-7-O-glucuronide reduces cytokine (IL-1β, IL-6) production. Oroxylin A-7-O-glucuronide exhibits anti-angiogenic, anti-tumor (glioma, liver cancer), anti-inflammatory, and hepatoprotective activities.

Cornuside is an iridoid glycoside with anti-allergic, anti-inflammatory, and neuroprotective activities. Cornuside exerts anti-allergic activity by downregulating the p38 MAPK, JNK, and NF-κB signaling pathways, and inhibits IgE-mediated histamine release from mast cells. Cornuside improves cognitive impairment in mice by inhibiting BACE1 activity (IC₅₀ = 55.84 μg/mL) and enhancing ChAT activity. Cornuside inhibits LPS (HY-D1056)-induced inflammatory mediators, including iNOS, COX-2, PGE2, TNF-α, IL-6, and IL-1β, by suppressing NF-κB activation.

TCS JNK 5a is a potent JNK3 inhibitor with a pIC₅₀ of 6.7. TCS JNK 5a also inhibits JNK2 with a pIC₅₀ of 6.5.

DB07268 is a potent and selective JNK1 inhibitor with an IC₅₀ value of 9 nM.

Gallic aldehyde (3,4,5-Trihydroxybenzaldehyde) is a phenolic aldehyde. Gallic aldehyde can be isolated from Geum japonicum. Gallic aldehyde inhibits the gelatinolytic activity and expression of MMP-9. Gallic aldehyde also inhibits ERK1/2, p38, and JNK. Gallic aldehyde has potent anti-HSV-1 and antioxidant activities. Gallic aldehyde also exhibits antibacterial activity against Oenococcus oeni VF.

Flavokawain A is a chalcone compound and an orally active inhibitor of PRMT5 and cytochrome P450. Flavokawain A has anti-inflammatory, anti-tumor, and immunomodulatory effects. Flavokawain A can inhibit the proliferation of tumor cells and induce apoptosis. Flavokawain A can be used in the research of diseases such as bladder cancer.

Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside is a TRPV1 antagonist and HDAC7 inhibitor. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside blocks TRPV1-mediated calcium influx, suppresses phosphorylation of p65, IκBα, p38, JNK, and ERK1/2, inhibiting NF-κB and MAPK signaling cascades. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside reduces production and gene expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside exhibits potent analgesic activity, elevates thermal pain threshold and mechanical pain threshold in murine models. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside restores CD8⁺ T cell infiltration into bladder cancer tumors and improves bladder cancer immunotherapy efficacy. Pinocembrin 7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-D-glucoside can be used for the researches of painand bladder cancer.

Loureirin B, a flavonoid extracted from Dracaena cochinchinensis, is an inhibitor of plasminogen activator inhibitor-1 (PAI-1), with an IC₅₀ of 26.10 μM; Loureirin B also inhibits K_ATP, the phosphorylation of ERK and JNK, and has anti-diabetic activity.

Silybin B (Silibinin B) is an orally active amyloid-β aggregation inhibitor and ATR pathway activator that can cross the blood-brain barrier. Silybin B inhibits Aβ fibril formation and promotes amorphous aggregate formation, while activating the ATR-mediated DNA damage repair pathway and inhibiting JNK/p38 MAPK signaling. Silybin B can reduce Cisplatin (HY-17394)-induced neuronal DNA damage and apoptosis. Silybin B has anti-oxidative stress, cell cycle regulation and neuroprotective activities. Silybin B is mainly used in the study of Alzheimer's disease and Cisplatin chemotherapy-related neurotoxicity.

DN-1289 is an orally active and selective inhibitor of dual leucine zipper kinase (DLK; IC₅₀=17 nM) and leucine zipper-bearing kinase (LZK; IC₅₀=40 nM). DN-1289 results significant attenuation of optic nerve crush (ONC)-induced p-c-Jun in mice model. DN-1289 has excellent in vivo plasma half-life and blood-brain barrier permeability.

Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC₅₀s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes.