p38α inhibitor 2

P38α Inhibitor 2, a potent and selective inhibitor of p38α MAPK, exhibits a pIC50 value of 9.6. It also demonstrates inhibition of the hERG ion channel (IC50=27 μM) and maintains promising selectivity, with <30% inhibition across a panel of 51 protein kinases at a 10 μM concentration and a broad specificity against 141 other biological targets[1].

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

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.

WH-4-023 (Dual LCK SRC inhibitor) is a potent and orally active Lck Src inhibitor. It also potently inhibits SIK.

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)

Zunsemetinib (ATI-450) is an orally active and selective inhibitor of the p38α mitogen-activated protein kinase-activated protein kinase 2 (MK2) pathway.Zunsemetinib is used to study spondyloarthritis and rheumatoid arthritis.

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 is a potent inhibitor of Lck and T cell proliferation. AMG-47a could promote the degradation of the KRAS oncoprotein. AMG-47a selectively reduced the levels of EGFP-KRASG12V protein but did not affect EGFP protein in cells.

Anti-inflammatory agent 33, a potent p38α inhibitor, effectively reduces NO production and suppresses LPS-induced expression of iNOS, COX-2, p-p38α, and p-MK2 proteins, thereby demonstrating anti-inflammatory activity.

(aS)-PH-797804 is a selective inhibitor of p38 MAPK, demonstrating inhibitory concentration (IC50) values of 26 nM for p38α and 102 nM for p38β. This compound exhibits anti-inflammatory activity [1] [2].

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].