p38α inhibitor 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。

Losmapimod (GSK-AHAB) 是一种可口服的特异性 p38 MAPK 抑制剂，抑制 p38α 和 p38β 的 pKi 值分别为 8.1 和 7.6。

AMG-548 hydrochloride is an orally active and selective p38α inhibitor (Ki: 0.5 nM) and shows slightly selective over p38β (Ki: 36 nM) and >1000 fold selective against p38γ p38δ. It is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC50: 3 nM).

AMG-548 is an orally active and selective p38α inhibitor (Ki=0.5 nM), shows slightly selective over p38β (Ki=36 nM) and >1000 fold selective against p38γ and p38δ and is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC50=3 nM

AMG-548 dihydrochloride is an orally active and selective p38α inhibitor (Ki: 0.5 nM) and shows slightly selective over p38β (Ki: 36 nM) and >1000 fold selective against p38γ p38δ. It is also extremely potent in the inhibition of whole blood LPS stimulate

Ralimetinib selectively inhibits phosphorylation of MK2 (Thr334) and has no effect on phosphorylation of p38α MAPK, JNK, ERK1 2, c-Jun, ATF2, or c-Myc. Ralimetinib is an effective and selective, ATP-competitive inhibitor of p38 MAPK α β (IC50s: 5.3 and 3.

p38α inhibitor 2 is a highly potent and selective p38α MAPK inhibitor, with a pIC50 of 9.6. p38α inhibitor 2 inhibits the hERG ion channel (IC50=27 μM) and shows a promising selectivity profile when tested in a panel of 51 other protein kinases (<30% inhibition at 10 μM concentration) and a panel of 141 other biological targets[1]. [1]. Raubo P, et al. The discovery and evaluation of 3-amino-2(1H)-pyrazinones as a novel series of selective p38α MAP kinase inhibitors [published online ahead of print, 2020 Jul 15]. Bioorg Med Chem Lett. 2020;30(18):127412.

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-IN-3 (Compound 2c) is a potent inhibitor of p38α MAPK, displaying antitumor properties by promoting apoptosis and increasing reactive oxygen species (ROS) production [1].

AMG-548 hydrochloride 是选择性的、口服具有活力的 p38α 抑制剂，Ki 值为 0.5 nM，对p38β略有选择性 (Ki=36 nM) 并且对 p38γ 和 p38δ 具有高于1000 倍的选择性。AMG 548 hydrochloride 同时能够有效抑制全血 LPS 刺激的TNFα，IC50值为 3 nM。AMG-548 hydrochloride 能够直接抑制酪蛋白激酶 1 (Casein kinase 1) 同种型 δ 和 ε ，进而对 Wnt 信号传导具有抑制作用。

AMG-548 dihydrochloride 是选择性的、口服具有活力的 p38α 抑制剂，Ki 值为 0.5 nM，对 p38β略有选择性 (Ki=36 nM) 并且对 p38γ 和 p38δ 具有 >1000 倍的选择性。AMG-548 dihydrochloride 对全血 LPS 刺激的 TNFα 表现出抑制作用，IC50 值为 3 nM。AMG-548 dihydrochloride 能够直接抑制酪蛋白激酶 1 (Casein kinase 1) 同种型 δ 和 ε ，并抑制 Wnt 信号传导。

WYE-687 是 ATP 竞争性的 mTOR 抑制剂，其 IC50=7 nM。它能够抑制PI3Kα和PI3Kγ，IC50分别为 81 nM 和 3.11 μM。它能够抑制mTORC1和mTORC2活化。

AS1940477 is p38 MAPK inhibitor. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms. In human peripheral blood mononuclear cells, AS1940477 inhibited lipopolysaccharide (LPS)- or phytohemagglutinin A (PHA)-induced production of proinflammatory cytokines, including TNFα, IL-1β, and IL-6 at low concentrations (LPS TNFα, IC(50)=0.45n M; PHA TNFα, IC(50)=0.40 nM). In addition, equivalent concentrations of AS1940477 that inhibited cytokine production also inhibited TNFα- and IL-1 β-induced production of IL-6, PGE(2), and MMP-3 in human synovial stromal cells. AS1940477 was also found to potently inhibit TNF production in whole blood (IC(50)=12 nM) and effectively inhibited TNFα production induced by systemically administered LPS in rats at less than 0.1mg kg (ED(50)=0.053 mg kg) with an anti-inflammatory effect lasting for 20h after oral administration. Overall, this stu......

AMG-47a 是具有口服活性的 Lck 抑制剂，IC50值为 0.2 nM。它具有抗炎作用，对 VEGF2、p38α、p38α、Jak3、MLR 和 IL-2的 IC50值分别为 1、3、72、30 和 21 nM。