JNK Inhibitor

RGB-286638 is a potent inhibitor of CDK and MAPK9. RGB-286638 inhibits the activities of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3 and p35-CDK5, with IC₅₀ values of 1, 2, 3, 4, 5 and 5 nM, respectively. RGB-286638 inhibits GSK-3β and TAK1, with IC₅₀ values of 3 nM and 5 nM, respectively. RGB-286638 induces caspase-dependent Apoptosis in cells. RGB-286638 delays tumor growth in an orthotopic glioblastoma mouse model. RGB-286638 extends survival in multiple myeloma models. RGB-286638 can be used in research related to glioblastoma and multiple myeloma.

2''-O-Galloylhyperin is an active natural compound with anti‑inflammatory, antioxidant, anti‑adipogenic, antifibrotic, and cytostatic activities. 2''-O-Galloylhyperin upregulates SIRT1/Nrf2 signaling, inhibits NF-κB and MAPK (ERK1/2, p38, JNK) phosphorylation, suppresses TSHR activation, reduces ROS accumulation, and enhances SOD and GSH-Px activities. 2''-O-Galloylhyperin protects against LPS-induced tissue injury, enhances survival, and inhibits adipogenesis and fibrosis. 2"-O-Galloylhyperin can be used for the research of sepsis, acute lung injury, and thyroid eye disease.

Inflachromene, a microglial inhibitor, binds to HMGB1 and HMGB2 and exerts anti-inflammatory effects. Inflachromene effectively downregulates proinflammatory functions of HMGB and reduces neuronal damage. Inflachromene can be used for the research of neuroinflammatory disorders.

Dehydrodiisoeugenol is an orally active anti-inflammatory and anti-tumor agent. Dehydrodiisoeugenol inhibits the proliferation of colorectal cancer cells, and induces apoptosis, autophagy, endoplasmic reticulum stress and cell cycle arrest. Dehydrodiisoeugenol also exerts anti-inflammatory effects by inhibiting the activation of NF-κB and the expression of COX-2. Dehydrodiisoeugenol can be used in the research related to colorectal cancer, inflammatory diseases and ulcerative colitis.

Ginkgo biloba extract is a natural product that can be isolated from Ginkgo biloba leaves. Ginkgo biloba extract alleviates oxidative stress-induced neuronal apoptosis (Apoptosis) by stabilizing mitochondrial function, regulating Bcl-2 family proteins and inhibiting caspase activation. Ginkgo biloba extract alleviates testicular injury by upregulating SKP2 and inhibiting Beclin1-independent autophagy (Autophagy). Ginkgo biloba extract alleviates various types of neuronal damage in animal models. Ginkgo biloba extract reduces behavioral sensitization in rats. Ginkgo biloba extract counteracts Aβ-induced neurotoxicity by blocking a series of Aβ-triggered events, including glucose uptake, ROS accumulation, AKT activation, mitochondrial dysfunction, JNK and ERK 1/2 pathways, and apoptosis, and also interferes with the formation of Aβ oligomers. Ginkgo biloba extract is applicable to research related to cerebral hypoperfusion, testicular injury, Alzheimer's disease, Parkinson's disease, multi-infarct dementia, stroke, traumatic brain injury and amyotrophic lateral sclerosis.

Halicin (SU3327) is a potent, selective and substrate-competitive JNK inhibitor with an IC₅₀ of 0.7 μM. Halicin also inhibits protein-protein interactions between JNK and JNK Interacting Protein (JIP) with an IC₅₀ of 239 nM. Halicin shows less active against p38α and Akt kinase.

Tamarixetin (4'-O-Methyl Quercetin) is an orally active natural flavonoid derivative of quercetin and caseinolytic protease p (ClpP) inhibitor with anti-inflammatory, antioxidant and antitumor effects. Tamarixetin inhibits the hydrolytic activity of ClpP to the fluorescent substrate Suc-LY-AMC with an IC₅₀ of 49.73 μM, which can be used for the study of Staphylococcus aureus infection. Tamarixetin inhibits tumor cell growth, induces apoptosis, and cell cycle arrest. Tamarixetin prevents cardiac hypertrophy by inhibiting the NFAT and AKT pathways.

(+)-Magnoflorine (α-Magnoflorine) iodide is an orally active aporphine alkaloid with multiple biological activities. (+)-Magnoflorine iodide promotes Parkin/PINK1 -mediated mitochondrial autophagy, inhibits the activation of NLRP3/Caspase-1 pathway, regulates the intestinal microbiota, and exhibits significant anti-inflammatory and immunomodulatory activities. (+)-Magnoflorine iodide inhibits JNK and TLR4/NF-κB signaling pathways, activates Sirt1/AMPK pathway, alleviates neuronal oxidative stress and apoptosis. Magnoflorine upregulates miR-410-3p, inhibits HMGB1/NF-κB pathway, and has anti-tumor activity. (+)-Magnoflorine iodide also has significant antifungal activity.

AS601245 is an orally active, selective, ATP competitive JNK (c-Jun NH2-terminal protein kinase) inhibitor with IC₅₀s of 150, 220, and 70 nM for three JNK human isoforms (hJNK1, hJNK2, and hJNK3), respectively. AS601245 exhibits 10- to 20-fold selectivity over c-src, CDK2, and c-Raf and more than 50- to 100-fold selectivity over a range of Ser/Thr- and Tyr-protein kinases. Neuroprotective properties.

Hordenine (Ordenina; Peyocactine) is a multifunctional alkaloid with oral activity and blood-brain barrier penetration. Hordenine inhibits LPS-induced phosphorylation of p38, JNK, ERK1/2, p65, IκB, and AKT, prevents p65 nuclear translocation, and suppresses inflammatory cytokines and mediators. Hordenine promotes M2 macrophage polarization, restores blood-milk barrier integrity, alleviates oxidative stress by reducing ROS and MDA, and attenuates LPS-induced lung injury and pulmonary edema. Hordenine inhibits cAMP production, CREB phosphorylation, and MITF expression, thereby suppressing melanin synthesis in melanocytes and reconstructed epidermis. Hordenine activates the Wnt/β-catenin signaling pathway, promotes dermal papilla cell proliferation and hair shaft elongation, and accelerates hair regeneration. Hordenine activates DRD2, acts as a D3R partial agonist, α2A-AR full agonist, and 5-HT2A-R antagonist, and inhibits SERT and DAT. Hordenine inhibits α-synuclein accumulation and ameliorates motor deficits in Parkinson's disease models. Hordenine limits alcohol intake, reduces relapse drinking behavior, and modulates alcohol-induced conditioned place preference. Hordenine can be used for research on mastitis, skin pigmentation, acute lung injury, foodborne diseases, hair loss, Parkinson's disease, bacterial infections, and alcohol use disorder.

BI-78D3 functions as a substrate competitive inhibitor of JNK, inhibit the JNK kinase activity (IC₅₀=280 nM).

Gamma-glutamylcysteine TFA (γ-Glu-Cys TFA) is an orally active, blood-brain barrier permeable dipeptide. Gamma-glutamylcysteine TFA activates AMPK, SIRT1, IL-4/STAT6, AC/cAMP/PI3K, IGF-1R/IRS1/PI3K, and Nrf2 signaling pathways; it inhibits NF-κB, JAK1/STAT1/3, MAPKs, cadmium-induced p38 MAPK, JNK, and PI3K/Akt signaling pathways. Gamma-glutamylcysteine TFA regulates macrophage polarization, modulates the trafficking of CD36 and GLUT4, induces glutathione synthesis, improves metabolic dysfunction, reduces lipid deposition, ameliorates glucose homeostasis, inhibits apoptosis (Apoptosis), stabilizes mitochondria, suppresses lipid peroxidation, iron accumulation and ferroptosis (Ferroptosis), reduces ds-HMGB1 levels, reverses mechanical hyperalgesia, and alleviates hepatic lipid droplet formation. Gamma-glutamylcysteine TFA is applicable to research related to inflammatory bowel disease, type 2 diabetes, cadmium-induced neurotoxicity, Alzheimer's disease, cerebral ischemia/reperfusion injury, neuropathy, and alcoholic liver disease.

Tomatidine hydrochloride acts as an anti-inflammatory agent by blocking NF-κB and JNK signaling. Tomatidine hydrochloride activates autophagy either in mammal cells or C elegans.

Sesamolin, isolated from Sesamum indicum, has antioxidative activity, Sesamolin inhibits lipid peroxidation and shows neuroprotection effect. Sesamolinl potently inhibits MAPK cascades by preventing phosphorylation of JNK, p38 MAPKs, and caspase-3 but not ERK-MAPK expression. Sesamolin is orally active.

Cenupatide (UPARANT) is a uPAR and FPR antagonist with anti-angiogenic, anti-inflammatory, and vascular barrier regulatory activities, as well as high stability and resistance to enzymatic degradation in blood/plasma. Cenupatide blocks the uPAR-FPR interaction, reduces VEGF-induced phosphorylation levels of AKT, VEGFR-2, STAT3, JNK, p38 MAPK, ERK1/2, and NF-κB p65, and inhibits αvβ3 integrin activation. Cenupatide suppresses endothelial cell migration, invasion, tube formation, and angiogenic signaling pathways, restores tight junctions and blood-retinal barrier integrity, reduces pro-inflammatory marker levels, and inhibits apoptosis. Cenupatide reduces retinal neovascularization, renal fibrosis, and vascular leakage, and restores visual function in preclinical models. Cenupatide is applicable to research related to retinopathy, diabetic complications, ocular diseases, cancer, and inflammatory diseases.

GNE-8505 is an orally active, blood-brain barrier-permeable selective dual leucine zipper kinase (DLK) inhibitor. GNE-8505 has an IC₅₀ of 0.144 μM for pJNK, and EC₅₀ of 0.457 μM for DRG. GNE-8505 inhibits the DLK/JNK pathway, reduces stress-induced c-Jun phosphorylation levels, decreases neuronal death and suppresses axonal degeneration. GNE-8505 reduces phosphorylated c-Jun levels in the retina, spinal cord and brain tissues of mice. GNE-8505 is applicable to research related to Alzheimer's disease and amyotrophic lateral sclerosis (ALS).

Matairesinol is an orally active bioactive compound with anti-inflammatory, antioxidant and anticancer activities. Matairesinol inhibits the phosphorylation of MAPK, JNK and NF-κB, downregulates RANKL-induced NFATc1 expression and activity, and suppresses the activation of the PI3K/AKT/FOXO1 pathway. Matairesinol can be used in research related to sepsis-mediated brain injury, osteoporosis, heart failure, atopic dermatitis and cancer.

Artemisinic acid (Qing Hao acid) is a sesquiterpene that can be isolated from Artemisia annua L. Artemisinic acid is also an important precursor for the synthesis of Artemisinin (HY-B0094). Artemisinic acid has various pharmacological activities, such as antimalarial activity, antitumor activity, antipyretic effect, antibacterial activity, allelopathic effect, and anti-adipogenic effect.

Pseudoginsenoside F11 is an orally active neuroprotective agent. Pseudoginsenoside F11 reduces the expression of β-amyloid precursor protein, inhibits the production of Aβ_1-40, downregulates the expression of JNK2, p53 and activated Caspase 3, and restores the activities of SOD and Glutathione peroxidase. Pseudoginsenoside F11 inhibits the excessive activation of μ-Calpain and restores the level of neuronal Nitric oxide synthase. Pseudoginsenoside F11 reduces infarct volume, alleviates cerebral edema, decreases neuronal loss, improves neurological deficits and enhances long-term functional outcomes in transient cerebral ischemia models. Pseudoginsenoside F11 antagonizes Methamphetamine-induced behavioral deficits, dopamine level reduction and neurotoxicity without altering the baseline behaviors of normal mice. Pseudoginsenoside F11 can be used in studies related to Alzheimer's disease, transient cerebral ischemic injury and Methamphetamine-induced neurotoxicity.

Methyl rosmarinate is an orally active hydroxycinnamic acid. Methyl rosmarinate exhibits an IC₅₀ of 24.70 μM and a K_i of 15.29 μM against PTP1B, an IC₅₀ of 41.46 μg/mL against BChE, a K_i of 0.61 mM against mushroom tyrosinase, and an IC₅₀ of 2.50 μM against SARS-CoV-2 3CLpro. Methyl rosmarinate downregulates the phosphorylation levels of ERK, JNK, p38, Smad2 and Smad3. Methyl rosmarinate activates erythrocyte BPGM and promotes the production of 2,3-BPG. Methyl rosmarinate induces apoptosis of fibroblasts. Methyl rosmarinate prolongs the survival time of hypoxic mice. Methyl rosmarinate improves insulin sensitivity. Methyl rosmarinate binds to SARS-CoV-2 3CLpro and inhibits viral replication. Methyl rosmarinate induces glioblastoma cell death. Methyl rosmarinate activates the TGR5/AMPK axis and reduces the levels of ROS and MDA. Methyl rosmarinate shows inhibitory activity against MMP-1. Methyl rosmarinate can be used in research related to pulmonary fibrosis, hypoxia-induced injury, type 2 diabetes, Alzheimer's disease, hyperpigmentation disorders, COVID-19, glioblastoma and myocardial ischemia-reperfusion injury.