IL-10 Modulator

MR-39 is a FPR2 agonist (EC₅₀ = 3.9 μM). MR-39 activates FPR2 to promote neuroinflammation resolution (downregulates IL-1β and TNF-α, modulates NF-κB), upregulates synaptic proteins (synaptic proteins) and improves dendritic spine morphology. MR-39 inhibits MAPK/ERK and AKT phosphorylation in glioblastoma, induces S-phase arrest, and suppresses migration, angiogenesis, and hypoxic adaptation. MR-39 reduces Aβ plaque burden via inhibiting MyD88/NF-κB and NLRP3 inflammasome. MR-39 can be used for research on autism spectrum disorder, Alzheimer's disease, and glioblastoma.

RO8323 is an orally active, selective CDK8/CDK19 inhibitor, with an IC₅₀ of 2 nM against CDK8 and 3 nM against CDK19. RO8323 promotes regulatory T cell differentiation, inhibits effector T cell generation, reverses the Teff/Treg ratio, upregulates IL-10 production in myeloid cells, and suppresses the production of TNF-α, IL-6 and IL-12. RO8323 enhances immune reconstitution and prolongs cardiac allograft survival in a dose-dependent manner. RO8323 can be used in the research of chronic graft-versus-host disease, cardiac allograft rejection, acute graft-versus-host disease and experimental autoimmune encephalomyelitis.

Tryptanthrin is an indole quinazoline that could be an alkaloid from indigo-bearing plants. Tryptanthrin is a potent and orally active cellular Leukotriene (LT) biosynthesis inhibitor. Tryptanthrin has anticancer activity. Tryptanthrin suppresses the expression levels of NOS1, COX-2, and NF-κB and regulates the expression levels of IL-2, IL-10, and TNF-α.

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.

Broussonin E is a phenolic compound and shows anti-inflammatory activity. Broussonin E can suppress inflammation by modulating macrophages activation statevia inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway. Broussonin E can be used for the research of inflammation-related diseases such as atherosclerosis.

Kaempferol 3-O-β-D-glucuronide (Kaempferol-3-glucuronide) is a metabolite of kaempferol that can be taken orally and has anti-inflammatory properties. Kaempferol 3-O-β-D-glucuronide can activate AKT/GSK3β phosphorylation and improve glucose metabolism.

Arabinoxylan Medium viscosity is an orally active Dectin-1 splice variant modulator, glucose absorption inhibitor, and chyme viscosity enhancer. Arabinoxylan Medium viscosity inhibits particulate β-glucan-induced Dectin-1A activation and mildly suppresses Dectin-1B activation. In human dendritic cells stimulated with particulate β-glucan, Arabinoxylan Medium viscosity reduces the production of IL-10 and TNF-α, and increases the production of IL-4 and IL-23. Arabinoxylan Medium viscosity also supports antifungal immune responses without activating TLR2, TLR4 or TLR5, and does not induce cytokine production when used to stimulate human dendritic cells alone. Arabinoxylan Medium viscosity increases small intestinal chyme viscosity, gets degraded in the large intestine to produce short-chain fatty acids, reduces glucose absorption and insulin response, and improves glucose homeostasis. Arabinoxylan Medium viscosity supports microbial fermentation and the growth of beneficial microbiota in the gastrointestinal tract, prevents bile acid reabsorption, and delays starch digestion. Arabinoxylan Medium viscosity can be used in research related to type 2 diabetes, impaired glucose tolerance, and metabolic syndrome.

LRH-1 agonist-2 (Compound 6N) is a selective, full LRH-1 agonist with an EC₅₀ of 15.7 nM. LRH-1 agonist-2 directly interacts with the Thr352 and His390 residues in the LRH-1 binding pocket, promotes allosteric signaling to the activation function surface (AFS), stabilizes the AFS and enhances coactivator recruitment. LRH-1 agonist-2 induces the anti-inflammatory cytokine IL-10, and reduces the pro-inflammatory cytokines IL-1β and TNFα. LRH-1 modulator-1 exerts anti-inflammatory effects in intestinal organoids. LRH-1 modulator-1 can be used in studies related to inflammatory bowel disease.

Graveoline (Rutamine) is an orally active alkaloid with various activities such as antifungal, antiparasitic, anti-inflammatory, and antitumor effects. Graveoline can induce tumor cell apoptosis and autophagy through a reactive oxygen species-mediated pathway. Graveoline has an MIC of 500 μg/mL for Candida albicans. Graveoline can be used in the research of various diseases such as tumors and liver injury.

GFH018 is an orally active, selective and ATP-competitive TGF-βR1 inhibitor with an IC₅₀ of 40 nM. GFH018 reactivates the immune system by blocking the immunosuppression mediated by regulatory T cells and M2 macrophages. GFH018 inhibits tumor angiogenesis. GFH018 suppresses tumor growth in mouse tumor models. GFH018 can be used for the research of solid tumors, hepatocellular carcinoma, colorectal cancer, breast cancer, and relapsed/metastatic nasopharyngeal carcinoma.

Ginsenoside F3 is a saponin extracted from the leaves of Panax ginseng with immunoenhancing and antitumor immunostimulatory activities. Ginsenoside F3 upregulates RIPOR2 with a K_d value of 3.77 μM. Ginsenoside F3 enhances NF‑κB activation, upregulates T‑bet and downregulates GATA‑3, increases the production of IL‑2 and IFN‑γ, decreases the production of IL‑4 and IL‑10, reverses CD8⁺ T‑cell exhaustion, restores cytokine secretion, and enhances antitumor immunity in a mouse non‑small cell lung cancer model. Ginsenoside F3 can be used for the research of non-small cell lung cancer.

γ-Hexalactone (γ-Caprolactone) is a gamma-lactone found in ripe fruits. γ-Hexalactone induces DNA damage in human lymphocytes and HepG2 cells, modulates cytokine secretion in human lymphocytes, and reduces recombinant PON1 activity. γ-Hexalactone serves as a dose-dependent oviposition inhibitor against Bactrocera oleae. γ-Hexalactone can be used for the research of Bactrocera oleae pest management.

PF-07899895 (Compound 34) is a SIK inhibitor, with IC₅₀ values of 1.2 nM, 0.9 nM, and 1.8 nM against SIK1, SIK2, and SIK3, respectively. PF-07899895 modulates the anti-inflammatory cytokine IL-10 in immune cells. PF-07899895 is applicable to research related to inflammatory diseases.

(E)-Methyl 4-coumarate (Methyl 4-hydroxycinnamate) is a phenolic compound and derivative of Cinnamic acid (HY-N0610A). (E)-Methyl 4-coumarate can be found in several plants, such as the leaves of Allium cepa and Morinda citrifolia L. (E)-Methyl 4-coumarate, when combined with Carnosic acid (HY-N0644), induces Apoptosis. (E)-Methyl 4-coumarate inhibits GSK3β activity and modulates inflammatory cytokine levels (increasing IL-10 and decreasing IL-4). (E)-Methyl 4-coumarate combined with Carnosic acid exhibits anticancer effects against acute myeloid leukemia. (E)-Methyl 4-coumarate ameliorates Plasmodium berghei NK65 infection.

Chitoheptaose is an orally active chitooligosaccharide (degree of polymerization = 7). Chitoheptaose can be extracted from the exoskeletons of crustaceans, such as the shells of crabs, shrimps and lobsters. Chitoheptaose reduces pro-inflammatory cytokines while increasing the levels of anti-inflammatory cytokines (decreasing the levels of pro-inflammatory cytokines IL-1β, IL-17A and IFN-γ, and increasing the level of the anti-inflammatory cytokine IL-10). Chitoheptaose possesses antioxidant, anti-inflammatory and anti-Apoptotic activities. Chitoheptaose improves cardiac parameters, alleviates myocarditis injury, and exerts cardioprotective effects in a rat model of myocarditis. Chitoheptaose can be used in studies related to myocarditis.

Laricitrin is a natural product with multiple biological activities. Laricitrin inhibits the phosphorylation and DNA-binding activity of STAT3, and downregulates the expression of IL-10. Laricitrin acts as an immunomodulator to regulate the differentiation, maturation and function of dendritic cells (DCs). Laricitrin inhibits the migration and invasion of lung cancer cells, and ameliorates lung cancer progression. Laricitrin can be used in research related to hypertension and lung cancer.

VO-OHPic is a reversible, noncompetitive PTEN inhibitor with an human IC₅₀ value of 46 nM. VO-OHPic inhibits PTEN signaling, activates Akt-GSK3β and Nrf-2/HO-1 pathways, induces apoptosis resistance and elevates IL-10 levels. VO-OHPic inhibits autophagy, ferroptosis and oxidative stress. VO-OHPic can be used for the research of acute myocardial infarction, intervertebral disc degeneration, cardiomyopathy and cancer.

2-ARA-LysoPtdEtn (1-Lyso-2-arachidonoyl-sn-glycero-3-phosphoethanolamine) is an orally active polyunsaturated acyl lysophosphatidylethanolamine. 2-ARA-LysoPtdEtn diminishes formation of LTC₄, LTB₄, and 12-HETE. 2-ARA-LysoPtdEtn lowers levels of IL-1β, IL-6, TNF-α, and NO. 2-ARA-LysoPtdEtn augments IL-10 levels and upgrades formation of 15-HETE and LXA₄. 2-ARA-LysoPtdEtn can be used for the research of peritonitis.

Lemairamin (Wgx-50) is a hydroxylamine compound. Lemairamin can be isolated from the pericarps of the Zanthoxylum plants. Lemairamin activates α7nAChR, stimulates the expression of IL-10 and POMC. Lemairamin shows a decrease in Akt. Lemairamin attenuates DSS-induced intestinal inflammation. Lemairamin alleviates pain hypersensitivity.

PNA5 is a novel, blood-brain barrier permeable glycosylated angiotensin-(1-7) peptide and MasR agonist. PNA5 inhibits IL-7, increases IL-10. PNA5 inhibits ROS generation, decreases Iba-1 expression. PNA5 exhibits sustained cognitive protective effects. PNA5 rescues blunted cerebral functional hyperemia. PNA5 can be used in the research of inflammation-related brain diseases.