mitogen-activated protein kinase 3

Isoquercetin (3-Glucosylquercetin) 是天然存在的多酚，具有抗氧化，抗增殖和抗炎特性。它通过调节核因子-κB 转录调节系统调节一氧化氮合酶 2 的表达。它通过 Nrf2 ARE 抗氧化剂信号传导途径减轻乙醇诱导的肝毒性，氧化应激和炎症反应。它具有高生物利用度和低毒性，是预防糖尿病妊娠出生缺陷的有希望的候选药物。

Vitexin 是一种存在于多种药用植物（如榕树、螺旋藻）中的 c-糖基化的黄酮。 它具有广泛的药理作用，包括抗氧化，抗癌，抗炎，抗痛觉过敏和神经保护作用。

MK2-IN-3 hydrate (MK-2 Inhibitor III) 是一种口服有活性的、ATP 竞争性的MAPKAP-K2 (MK-2)选择性抑制剂(IC50:0.85 nM)。

3-AP-Me 是 3-AP (SML0568) 的二甲基衍生物，作为核苷酸还原酶抑制剂。它能够通过磷酸化eIF2α和上调转录因子ATF4与ATF6基因表达，激活内质网 (ER) 应激途径，进而诱导细胞凋亡。此外，3-AP-Me 能够激活细胞应激激酶c-Jun N端激酶 (JNK) 和p38丝裂原活化蛋白激酶，还促进了可变剪接的mRNA变体XBP1的上调，在癌症领域的研究中有潜在用途。

RGB-286638 free base 是一种新型 CDK 抑制剂，抑制cyclin T1-CDK9、cyclin B1-CDK1、cyclin E-CDK2、cyclin D1-CDK4、cyclin E-CDK3和p35-CDK5活性，IC50分别为 1、2、3、4、5 和 5 nM。它也抑制 GSK-3β、TAK1、Jak2 和 MEK1，IC50值分别为 3、5、50和 54 nM。

Isorhamnetin (3-methylquercetin) 是从中草药沙棘中提取的一种类黄酮，可通过抑制MEK1和PI3K 来抑制皮肤癌。

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)

Sec-O-Glucosylhamaudol (Hamaudol 3-glucoside) 是从滨海前胡中分离得到的一种天然产物，能够降低 μ 阿片受体的蛋白水平，可用于缓解疼痛的研究。它通过调节脂多糖刺激的 RAW264.7 细胞系中的 p38 丝裂原活化蛋白激酶具有抗炎作用。

Pimasertib (AS703026) 是一种高效选择性和ATP 非竞争性的MEK1 2抑制剂，可用于癌症研究。

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].

p38α inhibitor 3是一种丝裂原活化蛋白激酶P38α的抑制剂，可以有效阻断成肌细胞分化。

LX-3 is a selective activator of the p38 mitogen-activated protein kinase (MAPK) pathway, which de-represses a subset of endogenous genes repressed by DNA methylation.

8-Gingerol 分离自姜的根状茎，是口服有效的 TRPV1激活剂，EC50值为5.0 µM。8-Gingerol 抑制 COX-2，还能抑制体外 H. pylori 的生长。

Olmutinib is a novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor, used in the treatment of T790M mutation positive non-small cell lung cancer. Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. EGFRs are frequently over-expressed in lung cancer and contribute to activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways which both promote cell survival and proliferation. By inhibiting EGFR activation, Olmutinib attenuates the activation of these tumor-promoting pathways. In the first phase I II clinical study of Osimertinib, 800 mg day was chosen as the dose for subsequent studies, and the dose-limiting toxicity and maximum tolerated dose was not reached. Olmutinib received breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.

HG-10-102-01 是富含亮氨酸重复激酶 2 和突变型G2019S 抑制剂，IC50分别为20.3 nM 和3.2 nM。

ERK1 2 inhibitor 3 是一种有效的 ERK1 2抑制剂。丝裂原活化蛋白激酶 (MAPK) 在信号转导通路中起着极其重要的作用，而细胞外信号调节激酶 (ERK) 是 MAPK 家族的成员。ERK1 2 inhibitor 3 具有研究或预防癌症、炎症或其他增殖性疾病的潜力。

3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles 具有多重生物活性，它是骨形态发生蛋白 2 (BMP2) 的抑制剂，展现了在 IC50 为 2.2 μM 的条件下的显效。同时，该化合物还能抑制丝裂原活化蛋白激酶 1 (MEK1)。此外，在 EAE 小鼠模型中，3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles 显示了其抗炎与神经保护的潜力。

MK2-IN-3 (MK2 Inhibitor III) 是选择性的 MAPKAP-K2 (MK-2)抑制剂(IC50:8.5 nM)，能够抑制 U937 细胞及体内 TNFα 的生成。

Klotho-derived peptide 1 (KP1 human) hydrochloride 能有效阻断 TGF-β 与 TGF-β receptor 2 的交互作用，并抑制由 TGF-β 引起的 Smad2 3 以及丝裂原活化蛋白激酶 (MAPK) 的激活。在小鼠模型中，该化合物展现了显著的抗纤维化效果以及对肾脏的保护作用。

Kamebakaurin (Kamebakaurine) 是一种提取自Isodon japonicus 中的天然产物，是一种NF-κB 的抑制剂，能够抑制 p50 的 DNA 结合活性。