Lucidone, an anti-inflammatory agent that can be isolated from the fruit of Lindera erythrocarpa Makino. Lucidone inhibits LPS-induced NO and PGE2 production in RAW 264.7 mouse macrophages. Lucidone also decreases TNF-α secretion, iNOS and COX-2 expression. Lucidone prevents NF-κB translocation and inhibits JNK and p38MAPK signals. Lucidone also has inhibitory activity against Dengue virus (DENV) (EC50=25 μM)[1][2].
Balanophonin is an anti-inflammatory and anti-cancer agent. Balanophonin inhibits microglial activation and neurodegeneration via inhibiting activated microglia-induced apoptosis[1].
PH-797804 is a novel pyridinone inhibitor of p38α with IC50 of 26 nM; 4-fold more selective versus p38β and does not inhibit JNK2.IC50 value: 26 nM [1]Target: p38αMAPKin vitro: PH-797804 blocks LPS-induced TNF-α production and p38 kinase activity in the human monocytic U937 cell line, with comparable IC50 of 5.9 nM and 1.1 nM. PH-797804 has no inhibitory effect on either the JNK pathway (c-Jun phosphorylation) or ERK pathway (ERK phosphorylation) in U937 cells at concentrations up to 1 μM. PH-797804 inhibits RANKL- and M-CSF-induced osteoclast formation in a concentration-dependent manner, with IC50 of 3 nM in primary rat bone marrow cells [1]. IC50 values for PH-797804 against the following targets have been determined to be greater than 200 μM (unless specified): CDK2, ERK2, IKK1, IKK2, IKKi, MAPKAP2, MAPKAP3, MKK7 (>100 μM), MNK, MSK (>164 μM), PRAK, RSK2, and TBK1, which means the activity of PH-797804 is specific [2]. in vivo: Orally dosing of PH-797804 effectively inhibits acute inflammatory responses induced by systemically administered endotoxin in both rat and cynomolgus monkeys. PH-797804 treatment for 10 days demonstrates robust anti-inflammatory activity in chronic disease models, significantly reducing both joint inflammation and associated bone loss in streptococcal cell wall-induced arthritis in rats and mouse collagen-induced arthritis. Dose-response analysis resulted in ED50 values of 0.07 mg/kg and 0.095 mg/kg in rat and cynomolgus monkeys, respectively. PH-797804 inhibits LPS-induced TNF-α, IL-6, and MK-2 activity in a dose- and concentration-dependent manner in a human endotoxin challenge model [1].
Dilmapimod (SB-681323) is a potent p38 MAPK inhibitor that potentially suppresses inflammation in chronic obstructive pulmonary disease.
Talmapimod (SCIO-469) is a selective ATP-competitive p38 inhibitor with IC50 of 9 nM for p38α.
p38 MAPK-IN-1 is a novel potent and selective inhibitor of p38 MAPK with IC50 of 68 nM, shows sustained levels, low clearance and good bioavailability.
Org OD 02-0 (10-Ethenyl-19-norprogesterone) is a membrane progesterone receptor α (mPRα)-specific agonist (IC50: 33.9 nM). Org OD 02-0 activates MAPK activity. Org OD 02-0 inhibits prolactin (PRL) secretion in the pituitary[1][2].
PD 169316 is a potent, cell-permeable and selective p38 MAP kinase inhibitor, with IC50 of 89 nM.
Isodorsmanin A is an anti-inflammatory agent. Isodorsmanin A suppresses the production of inflammatory mediators and proinflammatory cytokines. Isodorsmanin A inhibits the phosphorylation of JNK, MAPK[1].
BMS-582949 (compound 7k) is an orally active and highly selective p38α MAP kinase inhibitor, with IC50 values of 13 nM for p38α, and 50 nM for cellular TNFα. BMS-582949 can be used for research on rheumatoid arthritis[1].
Bisabolangelone, a sesquiterpene derivative, is isolated from the roots of Osterici Radix. Bisabolangelone possesses anti-inflammatory properties, which inhibits LPS-stimulated inflammation through the blocking of NF-kappaB and MAPK pathways in macrophages. Bisabolangelone has anti-ulcer activities[1][2].
PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC50 of 5.2 nM and a Ki of 3 nM. PF-3644022 also inhibits MK3 and p38 regulated/activated kinase (PRAK) with IC50s of 53 nM and 5.0 nM, respectively. PF-3644022 potently inhibits TNFα production and has anti-inflammatory effect[1].
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[1].
SB 203580 hydrochloride is a widely used p38 MAPK inhibitor with an IC50 of 0.3-0.5 μM. It shows more than 100-fold selectivity over PKB, LCK, and GSK-3β.
Esculin sesquihydrate, a fluorescent coumarin glucoside, is an active ingredient of ash bark. Esculin sesquihydrate ameliorates cognitive impairment in experimental diabetic nephropathy (DN), and exerts anti?oxidative stress and anti?inflammatory effects, via the MAPK signaling pathway[1][2].
PF-05381941 (PF 05381941, PF05381941) is a potent, dual TAK1/p38a inhibitor with IC50 of 156/186 nM respectively, with good kinome selectivity against 50 representative kinases; inhibits LPS-stimulated release of TNF-α from human peripheral mononuclear cells with IC50 of 8 nM.
Dihydrocaffeic acid is a phenolic acid found in Gynura bicolor, reduces phosphorylation of MAPK p38 and prevent UVB-induced skin damage. Antioxidant potential and anti-inflammatory activity[1].
p38 Kinase inhibitor 5 (AA6) is a potent p38 kinase inhibitor with an IC50 of 403.57 nM. p38 Kinase inhibitor 5 has anti-inflammatory activity[1].
Dehydromiltirone (1,2-Didehydromiltirone) is a diterpenoid quinone with an anti-inflammatory effect. Dehydromiltirone prevents liver injury by modifying the MAPK and NF-κB signaling pathways, reducing neuroinflammatory responses, and inhibiting platelet aggregation. Dehydromiltirone can be used for osteoporosis research[1][2].
PF-03715455 is a potent inhaled p38 MAPK inhibitor. PF-03715455 shows some selectivity for p38α over p38β with respective IC50 values of 0.88 and 23 nM. PF-03715455 potently inhibits LPS-induced TNFα production in human whole blood (IC50=1.7 nM). PF-03715455 has potential for the treatment of COPD (chronic obstructive pulmonary disease)[1][2].
(Rac)-Hesperetin is the racemate of Hesperetin. Hesperetin is a natural flavanone, and acts as a potent and broad-spectrum inhibitor against human UGT activity. Hesperetin induces apoptosis via p38 MAPK activation.
p38α inhibitor 4 (compound 10) is a selective and allosteric p38α inhibitor with an IC50 value of 1.2 μM. p38α inhibitor 4 exhibits no activity against p38β, p38γ, and p38δ[1].
Anti-inflammatory agent 33 is a potent p38α inhibitor. Anti-inflammatory agent 33 inhibits NO production. Anti-inflammatory agent 33 inhibits LPS-induced iNOS, COX-2, p-p38α, p-MK2 protein expression. Anti-inflammatory agent 33 shows anti-inflammatory activity[1].
SB 706504 is a potent p38 MAPK inhibitor that inhibits Lipopolysaccharides (HY-D1056)-stimulated inflammatory gene expression in macrophages in chronic obstructive pulmonary disease (COPD)[1].
ITX5061 is a type II inhibitor of p38 MAPK and also an antagonist of scavenger receptor B1 (SR-B1).
Atraric acid (Methyl atrarate) is a specific androgen receptor (AR) antagonist with anti-inflammatory and anticancer effects. Atraric acid represses the expression of the endogenous prostate specific antigen gene in both LNCaP and C4-2 cells. Atraric acid can also inhibit the synthesis of NO and cytokine, and suppress the MAPK-NFκB signaling pathway. Atraric acid can be used to research prostate diseases and inflammatory diseases[1][2].
6,8-Diprenylorobol, a prenylated isoflavone, is a nature product that could be isolated from the leaves of Cudrania tricuspidata. 6,8-Diprenylorobol antiproliferative effect and induces apoptosis through activation of p53 and generation of ROS[1][2].
Nitidine chloride, a potential anti-malarial lead compound derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through diverse pathways, including inducing apoptosis, inhibiting STAT3 signaling cascade, DNA topoisomerase 1 and 2A, ERK and c-Src/FAK associated signaling pathway. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kB pathway[1][2][3][4][5][6].
SKF-86002 dihydrochloride is an orally active p38 MAPK inhibitor, with anti-inflammatory, anti-arthritic and analgesic activities. SKF-86002 dihydrochloride inhibits lipopolysaccharide (LPS)-stimulate human monocyte IL-1 and TNF-α production (IC50 = 1 μM). SKF-86002 dihydrochloride inhibits lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid[1][2][3].
Losmapimod is a selective, potent, and orally active p38 MAPK inhibitor with pKis of 8.1 and 7.6 for p38α and p38β, respectively.