p38 mapk in 1

p38 MAPK-IN-1 是一种新型的选择性 p38 MAPK 抑制剂，具有高效（ IC50 ＝68 nM）、长效和低清除率的特点，通过抑制 LPS 诱导的 TNF-α 产生从而降低炎症反应。

ERK2 p38α MAPK-IN-1 (Compound 1, In silico Hit-2) 表现为一种对ERK2和p38αMAPK具有高效和选择性的抑制作用，其中对ERK2的抑制半最大浓度（IC50）为82 μM。该化合物通过与ERK2和p38αMAPK的构象位点不同地结合来实现其抑制效果。ERK2 p38α MAPK-IN-1 主要用于2型糖尿病相关的生物医学研究。

p38αMAPK CK1δ inhibitor-1 (Compound 3) 对 p38αMAPK 和 CK1δ 的抑制活性分别是 IC50=0.185 µM 和 IC50=0.089 µM。

p38-α MAPK-IN-1 是一种 MAPK14 (p38-α) 抑制剂，在 EFC 置换试验和 HTRF 试验中 IC50 分别为 2300 nM 和 5500 nM。

Dehydrocorydaline (13-Methylpalmatine) 是一种生物碱。它调节Bax，Bcl-2蛋白表达，激活caspase-7，caspase-8，并使PARP 失活。它能增强p38 MAPK 活化，具有抗炎、抗癌等功效。它具有强大的抗疟疾作用，并具低细胞毒性。

Fumaric acid (2-Butenedioic acid) 与烟酸酶缺乏症相关，是癌症相关的内源性代谢物。

Flavokawain A (Flavokavain A) 是 kava 提取物中的查耳酮，是一种抗癌试剂，具有抗肿瘤活性。它通过 Bax 蛋白依赖和线粒体依赖的凋亡途径诱导细胞凋亡，有潜力用于膀胱癌的相关研究。

Caffeic Acid Phenethyl Ester (Phenylethyl Caffeate) 是咖啡酸的苯乙醇酯，是蜂巢蜂胶的生物活性成分。它抑制核转录因子 NF-kappa B 的激活，具有抗肿瘤、细胞保护和免疫调节活性。它抑制 PDGF 诱导的血管平滑肌细胞增殖。

SKF-86002 是一种可口服的 p38 MAPK 抑制剂，具有抗炎和抗关节炎活性，可用于缓解疼痛的研究。它能抑制脂氧合酶和环氧合酶介导的花生四烯酸代谢，还抑制脂多糖 (LPS) 刺激人单核细胞产生 IL-1 和 TNF-α，IC50为 1 μM。

Cornuside (Comuside) 是从山茱萸的果实中分离出的环烯醚萜苷，可用于炎症疾病的研究和促进血液循环。 它通过下调 MAPK 和 NF-κB 信号通路抑制肥大细胞介导的过敏反应，用于炎性过敏性疾病中的潜能。

MAPK13-IN-1 是一种有效的 MAPK13 (p38δ) 抑制剂（IC50：620 nM）。

Saikosaponin A 是银柴胡中的主要活性成分，有抗炎活性，可上调 LXRα的表达。

Dehydrocorydaline nitrate 是生物碱。Dehydrocorydaline 调节 Bax，Bcl-2蛋白表达，激活 caspase-7，caspase-8，并使 PARP 失活。它能增强 p38 MAPK 活化，具有抗炎、抗癌、抗疟疾等功效。

(±)14(15)-EET is a metabolite of arachidonic acid that is formed via epoxidation of arachidonic acid by cytochrome P450.[1],[2] It prevents increases in leukotriene B4, ICAM-1, and chemokine (C-C motif) ligand 1 (CCL2) induced by oxidized LDL in primary rat pulmonary artery endothelial cells (RPAECs) when used at a concentration of 1 μM.[3] (±)14(15)-EET induces dilation of preconstricted isolated canine coronary arterioles (EC50 = 0.2 pM).[4] It reduces myocardial infarct size as a percentage of the area at risk in a canine model of ischemia-reperfusion injury induced by left anterior descending coronary artery (LAD) occlusion when administered at a dose of 0.128 mg kg prior to occlusion or reperfusion.[5] Reference：[1]. Chacos, N., Falck, J.R., Wixtrom, C., et al. Novel epoxides formed during the liver cytochrome P-450 oxidation of arachidonic acid. Biochem. Biophys. Res. Commun. 104(3), 916-922 (1982).[2]. Oliw, E.H., Guengerich, F.P., and Oates, J.A. Oxygenation of arachidonic acid by hepatic monooxygenases. Isolation and metabolism of four epoxide intermediates. J. Biol. Chem. 257(7), 3771-3781 (1982).[3]. Jiang, J.-X., Zhang, S.-J., Xiong, Y.-K., et al. EETs attenuate ox-LDL-induced LTB4 production and activity by inhibiting p38 MAPK phosphorylation and 5-LO BLT1 receptor expression in rat pulmonary arterial endothelial cells. PLoS One 10(6), e0128278 (2015).[4]. Oltman, C.L., Weintraub, N.L., VanRollins, M., et al. Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ. Res. 83(9), 932-939 (1998).[5]. Nithipatikom, K., Moore, J.M., Isbell, M.A., et al. Epoxyeicosatrienoic acids in cardioprotection: Ischemic versus reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 291(2), H537-H542 (2006).

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

Globotetraosylceramides are bioactive neutral glycosphingolipids. They are the major glycolipids in human erythrocytes. They act as receptors for the Shiga toxins Stx1, Stx2, and Stx2e, the cytotoxic protein pierisin-1, and parvovirus B19. Globotetraosylceramides increase the expression of proteins responsible for enamel deposition, including ameloblastin, amelogenin, and enamelin, in dental epithelial cells and activate the ERK and p38 MAPK signaling pathways. Levels of globotetraosylceramides are elevated in fibroblasts from patients with salt and pepper syndrome, a neurocutaneous condition characterized by intellectual disability and hyper- and hypo-pigmented skin. Globotetraosylceramides (porcine RBC) contains a mixture of globotetraosylceramides with variable fatty acyl chain lengths isolated from porcine red blood cells.

Verrucarin A (Muconomycin A) 是一种 D 型大环真菌毒素。Verrucarin A 是一种蛋白质合成 (protein synthesis) 的抑制剂，来源于Myrothecium verrucaria，可抑制白血病细胞系生长，并激活巨噬细胞 caspases、凋亡和炎症信号。Verrucarin A 能有效提高 p38 MAPK 的磷酸化，降低 ERK Akt 的磷酸化。Verrucarin A 通过 p21 和 p53 的诱导引起细胞周期调控的解除。

12(S)-HHT(12(S)-HHTrE)是通过环氧化酶（COX）的花生四烯酸代谢途径生成的脂肪酸，是BLT2的内源性配体和激动剂，12(S)-HHT BLT2轴在维持上皮组织稳态方面和炎症反应中起作用。12-HHT通过上调MKP-1抑制p38 MAPK NF-κB通路，导致UVB照射的HaCaT细胞的IL-6合成减少。

CK1-IN-1 (PUN51207) 是一种酪蛋白激酶 1 抑制剂，对 CK1δ、CK1ε和p38σ MAPK 的IC50值为 15 nM、16 nM 和73 nM。

Triptonide (PG 492) 是从雷公藤中鉴定出的一种天然产物，是一种 Wnt 信号抑制剂，其 IC50约为 0.3 nM。它具有免疫抑制、抗炎、避育、神经保护和抗淋巴瘤作用。

Sesaminol 是从Justicia orbiculata 中分离得到的一种天然产物，抑制脂质过氧化，具有神经保护作用和抗氧化活性。它通过抑制JNK、p38 MAPKs 和caspase-3磷酸化，抑制MAPK 的级联反应。

p38-α MAPK-IN-4 (Compound 69) 是一种选择性的p38α MAPK 抑制剂，IC50为 1.5 μM。p38-α MAPK-IN-4 在体内可快速、强烈地抑制机械性触诱发痛 (mechanical allodynia) 的发生。