Mitogen-activated protein kinase 1

Mitogen-activated protein kinase 1 (MAPK1) activates the p38/NF-κB pathway and regulates cellular processes in sepsis-associated diseases. Its catalytic action phosphorylates substrate proteins, serving as a regulatory switch for their activity [1].

1. Isoquercetin (3-Glucosylquercetin) is a potential stimulator of bone mineralization used for prophylaxis of osteoporotic disorders. 2. Isoquercetin may be as a potential therapeutic agent against neurodegeneration in Parkinson's disease. 3. Isoquercetin is an inhibitor of Wnt/β-catenin and may be as a potential novel anti-tumoral agent, such as against human pancreati,liver cancer related to opioid receptors and to the activation of the mitogen-activated protein kinase (MAPK) signalling pathway. .

Caffeic Acid Phenethyl Ester (Phenylethyl Caffeate) (CAPE) inhibits the activation of nuclear transcription factor NF-kappa B and may suppress p70S6K and Akt-driven signaling pathways, with antineoplastic, cytoprotective and immunomodulating activities. CAPE is the phenethyl alcohol ester of caffeic acid and a bioactive component of honeybee hive propolis. In addition, CAPE inhibits PDGF-induced proliferation of vascular smooth muscle cells through the activation of p38 mitogen-activated protein kinase (MAPK) and hypoxia-inducible factor (HIF)-1alpha and subsequent induction of heme oxygenase-1 (HO-1).

CMPD1 is a non-ATP-competitive p38 MAPK-mediated MK2 phosphorylation inhibitor(apparent Ki (Kiapp): 330 nM).

Bufalin is a natural product and a Na⁺/K⁺-ATPase inhibitor (IC50 ≈ 40–45 nM) with favorable cell permeability. By binding to α subunits such as ATP1A1, bufalin induces calcium overload and pyroptosis, and can be used for experimental research and therapeutic exploration in various cancers.

SL327 is a selective inhibitor for MEK1/2 with IC50 of 0.18 μM/0.22 μM; able to transport through the blood-brain barrier.

BAY1143269 is an orally effective mitogen-activated protein kinase-interacting serine/threonine-protein kinase 1 (MKNK1) inhibitor with potential anti-tumor activity.

Tomivosertib (eFT508) is a potent and highly selective MNK1 and MNK2 inhibitor with an IC50 value of 1-2 nM.

A2ti-1 is a highly selective inhibitor of annexin A2/S100A10 heterotetramer (A2t) (IC50: 24 μM) that inhibits ARV-mediated activation of Src and p38 mitogen-activated protein kinase (MAPK). A2ti-1 can be used to study human papillomavirus type 16 (HPV16) infection.

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

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

Isoacteoside has the anti-inflammatory effect, mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways.

FgGpmk1-IN-1 is a new inhibitor of the fusarium graminearum mitogen-activated protein kinase (FgGpmk1), displaying a potency with an EC50 value of 3.46 μg/mL.

MK2-IN-1 hydrochloride (MK 25) is a highly selective, non-ATP competitive inhibitor of p38/mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2 or MK2, IC50: 0.11 μM) [1].

The growth factors, platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) play major roles in enhanced smooth muscle cells growth in rodent blood vessels after vascular injury. Tyrosine kinase inhibition has been shown to be effective in blocking tyrosine phosphorylation at the PDGF and bFGF receptors in cultured fibroblast and vascular smooth muscle cells which in turn inhibits their proliferation[1]. CGP 53716 is a specific PDGFR tyrosine kinase inhibitor on SMC (smooth muscle cell) proliferation and migration in vitro and in neointimal formationin vivo[3]. CGP 53716 inhibited serum-induced cell growth in RASMC (rat aortic smooth muscle cells). And it completely blocked PDGF-BB tyrosine receptor autophosphorylation in RASMC and 3T3 cells, PDGF-BB-induced phosphorylation of mitogen-activated protein kinase at 1 μM in RASMC and inhibited PDGF-BB-induced c-Fos protein expression at 1 μM in RASMC; consistent with inhibition of PDGF-BB-induced DNA synthesis. Further, CGP 53716 inhibited PDGF-BB-, bFGF- and EGF-induced DNA synthesis in a concentration-dependent manner in each cell line. And it showed a 2- to 4-fold selectivity for PDGF-BB-stimulated DNA synthesis over bFGF or EGF in RASMC or 3T3 cells[1]. CGP 53716 inhibited dose dependently tyrosine phosphorylation of both the known PDGFRs: the PDGFR-α and PDGFR-β. After rat carotid artery ballooning injuryin vivo, the migration of alpha-actin-positive cells on the luminal side of internal elastic lamina was decreased with 50 mg/kg/day of CGP 53716 from 38 ± 10 (control group) to 4 ± 2. Intima/media ratio was inhibited by 40% after 14 days in the CGP 53716-treated group (P=0.028) after rat aortic denudation[3].

GDC-0623 (RG 7421) is a potent, ATP-uncompetitive MEK1 inhibitor with a Ki of 0.13 nM, currently in Phase 1.

1. Vitexin has antinociceptive and antispasmodic activities. 2. Vitexin exhibits a prominent first-pass effect. 3. Vitexin has antioxidant, antimyeloperoxidase, and α-glucosidase inhibitory activities. 4. Vitexin can either inhibit or induce activities of

1. 8-Gingerol has antioxidant activity. 2. 8-Gingerol has antimycobacterial activity. 3. 8-Gingerol could be used as an effective skin-whitening agent. 4. 8-Gingerol shows antipyretic and anti-inflammation characteristics. 5. 8-Gingerol seems to be effect

ERK1/2 Inhibitor 3, a potent inhibitor of ERK1/2, plays a crucial role in the signal transduction pathway by targeting the Mitogen-activated protein kinase (MAPK) family, specifically the extracellular signal-regulated kinase (ERK). Given its significant impact, this compound holds promise for research or prevention efforts related to cancer, inflammation, or other proliferative diseases[1].

MMI-0100, a cell-permeant peptide inhibitor of mitogen-activated protein kinase activated protein kinase II (MK2), effectively reduces intimal hyperplasia ex vivo and in vivo. It specifically suppresses IL-6 expression while not affecting IL-8 expression and mitigates fibrotic processes, including vein graft disease [1].

P34cdc2 Kinase Fragment plays a crucial role in yeast mitosis by ensuring the completion of DNA replication and regulates microtubule polymerization in Xenopus oocytes meiosis by phosphorylating mitogen-activated protein 2 (MAP2) [1] [2].

N-Arachidonoyl-L-serine (ARA-S), a recently isolated endocannabinoid with a distinct activity profile that diverges from typical endocannabinoids, does not interact with central cannabinoid (CB1), peripheral cannabinoid (CB2) receptors, or vanilloid receptor 1 (VR1). Unlike other compounds, ARA-S (5 mg/kg) counteracts the lowering of blood pressure induced by a 10 mg/kg intravenous bolus of abnormal cannabidiol (Abn-CBD) in anesthetized rat models. Additionally, akin to Abn-CBD, ARA-S induces relaxation in isolated rat mesenteric arteries and abdominal aorta and promotes phosphorylation of Akt and mitogen-activated protein kinase (MAPK) in human umbilical vein endothelial cells (HUVEC). The mechanisms through which ARA-S and Abn-CBD exert their effects on vascular systems show variations and merit deeper investigation.

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

Ganoderiol F has anti-inflammatory, cytotoxic and anti-HIV activity, it inhibits activity of topoisomerases in vitro, and it inhibits human immunodeficiency virus-1 protease with IC(50) values of 20-40 microM. It induced HO-1 expression, activation of the mitogen-activated protein kinase EKR and up-regulation of cyclin-dependent kinase inhibitor p16 and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production.