p38-α mapk-in-1

p38-α MAPK-IN-1 is a MAPK14 (p38-α) inhibitor with an IC50 of 2300 nM in the EFC displacement assay and 5500 nM in the HTRF assay.

BChE/p38-α MAPK-IN-1 is a selective dual inhibitor targeting hBChE (IC50 = 772 nM) and p38α MAPK (IC50 = 191 nM). It reduces the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) in cells, improves scopolamine-induced cognitive impairment, alleviates LPS-induced spatial learning deficits, and exhibits anti-neuroinflammatory effects in mice, making it applicable for Alzheimer's disease (AD) research.

p38-α MAPK-IN-10 (Compound 6) is an inhibitor of p38α, with an IC50 value of 4 nM.

p38-α MAPK-IN-11 (Compound 4C) is a selective blood-brain barrier-penetrable inhibitor of P38α MAPK, with an IC50 of 43 nM. It exhibits minimal inhibitory activity against other MAPK isoforms, such as p38β, p38γ, and p38δ, with IC50 values of > 100 nM, > 100 nM, and 48.6 mM, respectively. In rat models resembling Alzheimer’s disease, p38-α MAPK-IN-11 demonstrates significant neuroprotective and anti-neuroinflammatory effects. This compound is valuable for Alzheimer's disease research.

p38 MAPK-IN-1 is a novel selective p38 MAPK inhibitor with high potency, long duration, and low clearance, which reduces inflammatory responses by inhibiting LPS-induced TNF-α production.

p38 MAPK-IN-10 (Compound 4) is an orally active and potent inhibitor of p38 MAP kinase, with an IC50 of 570 nM. It shows promise for research into chronic inflammatory diseases, including rheumatoid arthritis and Crohn's disease.

ERK2/p38α MAPK-IN-1 (Compound 1, In silico Hit-2), a selective inhibitor of ERK2 and p38α MAPK, exhibits potent activity with an IC 50 of 82 μM against ERK2. It uniquely binds to the allosteric sites of both ERK2 and p38α MAPK. This compound is utilized for type 2 diabetes research [1].

Fumaric acid (2-Butenedioic acid) attenuates the eotaxin-1 expression in TNF-α-stimulated fibroblasts by suppressing p38 MAPK-dependent NF-κB signaling. Fumaric acid has recently been identified as an oncometabolite or an endogenous, cancer-causing metabolite. High levels of this organic acid can be found in tumors or biofluids surrounding tumors. Its oncogenic action appears due to its ability to inhibit prolyl hydroxylase-containing enzymes.

SKF-86002 is an effective inhibitor of p38 MAP kinase (IC50: 0.5-1 uM); inhibits LPS-induced IL-1 and TNF-α production in human monocytes (IC50: 1 μM).

Saikosaponin A has a variety of pharmacological benefits, including antiepileptic, anti-osteoporosis, antioxidant, anti-in ammatory, immunomodulatory, and anti-bacterial activities. It can effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of p38 MAPK and NF-κB signaling pathways in spinal cord. It can inhibit NMDA receptor current and persistent sodium current, and inhibit the TNF-α level, the IL-1β production, and cysteine-aspartic acid protease (caspase)-1 activity.

Tpl2 kinase inhibitor is an inhibitor of tumor progression locus 2 (Tpl2; IC50= 0.05 μM).1It is selective for Tpl2 over MEK, p38 MAPK, Src, MK2, and PKC (IC50s = >40, 180, >400, 110, and >400 μM, respectively). Tpl2 kinase inhibitor inhibits LPS-induced TNF-α production in isolated human monocytes and whole blood (IC50s = 0.7 and 8.5 μM, respectively). It enhances differentiation induced by calcitriol in HL-60 and U937 leukemia cells when used at a concentration of 5 μM.2Tpl2 kinase inhibitor (5 μM) inhibits the proliferation of KG-1a leukemia cells.3 1.Garvin, L.K., Green, N., Hu, Y., et al.Inhibition of Tpl2 kinase and TNF-α production with 1,7-naphthyridine-3-carbonitriles: Synthesis and structure-activity relationshipsBioor. Med. Chem. Lett.15(23)5288-5292(2005) 2.Wang, X., and Studzinski, G.P.Expression of MAP3 kinase COT1 is up-regulated by 1,25-dihydroxyvitamin D3 in parallel with activated c-jun during differentiation of human myeloid leukemia cellsJ. Steroid. Biochem. Mol. Biol.121(1-2)395-398(2010) 3.Wang, X., Gocek, E., Novik, V., et al.Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D3Cell Cycle9(22)4542-4551(2010)

p38 MAPK inhibitor IV is an ATP-competitive inhibitor of p38 MAP kinases with IC50 values of 0.13, 0.55, 5.47, and 8.63 μM for p38α, p38β, p38x, and p38δ, respectively, in vitro.[1] It also inhibits LPS-induced TNF-α and IL-1β cytokine production (IC50s = 22 and 44 nM, respectively) in human peripheral blood mononuclear cells.

p38 MAPK inhibitor (IC50 = 0.38 μM). Inhibits the release of IL-1β and TNF-α in a peripheral blood mononuclear cell (PBMC) assay (IC50 values are 0.039 and 0.16 μM respectively). Laufer et al (2003) Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J.Med.Chem. 46 3230 PMID:12852754 |Kammerer et al (2007) Pharmacokinetics of ML3403 ({4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-(1-phenylethyl)-amine), a 4-pyridinylimidazole-type p38 mitogen-activated protein kinase inhibitor. Drug Metab.Dispos. 35 875 PMID:17344341

p38-α MAPK-IN-4 (Compound 69) is a selective inhibitor of p38α MAPK, with an IC50 of 1.5 μM, and effectively mitigates the onset of mechanical allodynia (MA) in vivo [1].

1. Sauchinone is a useful adjunctive treatment for bacterial infection. 2. Sauchinone, an active lignan found in Saururus chinensis, to regulate the activation of HSCs, to prevent liver fibrosis, and to inhibit oxidative stress in vivo and in vitro. 3. Sa

Semapimod is an inhibitor of proinflammatory cytokine production, capable of suppressing TNF-α, IL-1β, and IL-6. It hinders TLR4 signaling with an IC50 of approximately 0.3 μM, impedes p38 MAPK, and reduces nitric oxide production in macrophages. This compound shows promise for treating various inflammatory and autoimmune disorders [1] [2] [3].

p-Synephrine is a naturally occurring protoalkaloid used as a dietary supplement in the field of weight management. Mechanistically, compared to ephedrine and n-synephrine, p-synephrine exhibits weaker binding affinity for α-1, α-2, β-1, and β-2 adrenergic receptors at commonly used doses and does not demonstrate significant sympathomimetic activity. Furthermore, recent in vitro cellular studies have shown that p-Synephrine possesses antioxidant activity and exerts anti-inflammatory effects by downregulating the p38 MAPK/NF-κB signaling pathway.

Compound 3a (p38-α MAPK-IN-6) is an inhibitor of the p38α mitogen-activated protein kinase [1].

Saikosaponin A (Standard) is a reference standard for research and analysis in studies involving Saikosaponin A. Saikosaponin A has a variety of pharmacological benefits, including antiepileptic, anti-osteoporosis, antioxidant, anti-in ammatory, immunomodulatory, and anti-bacterial activities. It can effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of p38 MAPK and NF-κB signaling pathways in spinal cord. It can inhibit NMDA receptor current and persistent sodium current, and inhibit the TNF-α level, the IL-1β production, and cysteine-aspartic acid protease (caspase)-1 activity.

Fumaric acid (Standard) is the standard substance of Fumaric acid, and it is applicable for quantitative analysis, quality control, and related research in biochemical experiments. Fumaric acid (2-Butenedioic acid) attenuates the eotaxin-1 expression in TNF-α-stimulated fibroblasts by suppressing p38 MAPK-dependent NF-κB signaling. Fumaric acid has recently been identified as an oncometabolite or an endogenous, cancer-causing metabolite. High levels of this organic acid can be found in tumors or biofluids surrounding tumors. Its oncogenic action appears due to its ability to inhibit prolyl hydroxylase-containing enzymes.

Sauchinone (Standard) is a reference standard for research and analysis in studies involving Sauchinone. 1. Sauchinone is a useful adjunctive treatment for bacterial infection. 2. Sauchinone, an active lignan found in Saururus chinensis, to regulate the activation of HSCs, to prevent liver fibrosis, and to inhibit oxidative stress in vivo and in vitro. 3. Sauchinone diminishes LPS-induced neutrophil activation and acute lung injury. 4. Sauchinone-induced HO-1 expression plays a key role in the vascular protective effects of Sauchinone in HUVEC. 5. Sauchinone protects skin keratinocytes through inhibition of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK signaling via upregulation of oxidative defense enzymes.

Cnidilide is a natural alkyl phthalide compound that can be isolated from the rhizomes of Cnidium officinale. It reduces the production of NO and PGE2 by inhibiting LPS-induced expression of iNOS and COX-2. Additionally, Cnidilide suppresses the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. It specifically inhibits the phosphorylation of p38 MAPK and JNK, as well as the activation of downstream kinase MSK-1. Moreover, Cnidilide blocks signaling pathways by inhibiting the transcriptional activities of AP-1 and NF-κB. This compound is useful in the study of inflammatory diseases.

Trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A- α protein. Trichosanatine can alleviate oxidized low-density lipoprotein induced endothelial cells injury via inhibiting the LOX-1/p38 MAPK pathway.