erk5 in 1

ERK5-IN-1 is a potent ERK5 inhibitor (IC50: 87 nM) and also inhibits LRRK2[G2019S] (IC50: 26 nM).

XMD17-109 (ERK5-IN-1) is a new selective ERK-5 inhibitor (EC50: 4.2 uM, HEK293 cells).

L-797,591 hydrochloride is active for somatostatin receptor isoform 1 (SSTR1). L-797,591 hydrochloride is commonly used in combination with AG1478 to enhance p-ERK5 expression in SSTR1 cells. L-797,591 hydrochloride significantly enhanced p38 phosphorylation in cotransfected cells, and this effect was reversed in combination with AG1478.

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)

ADTL-EI1712 is a dual inhibitor of ERK1 and ERK5 (IC50s = 40.43 and 64.5 nM, respectively).1It reduces ERK1 and ERK5 activity by 93.5% and 89.4%, respectively, but also inhibits ERK2 activity by 92.7%, in a panel of 100 kinases at 1 μM. ADTL-EI1712 inhibits proliferation of HL-60 and MKN74, but not HeLa, cancer cells (IC50s = 1.26, 2.55, and >50 μM, respectively). It reduces tumor growth and intratumor phosphorylation of ERK1/2 and ERK5 in an MKN74 mouse xenograft model when administered at a dose of 50 mg/kg per day. 1.Wang, G., Zhao, Y., Liu, Y., et al.Discovery of a novel dual-target inhibitor of ERK1 and ERK5 that induces regulated cell death to overcome compensatory mechanism in specific tumor typesJ. Med. Chem.63(8)3976-3995(2020)

ERK5-IN-4 (compound 34b) is a potent and specific inhibitor of extracellular signal-related kinase 5 (ERK5) activity, effectively inhibiting both full-length ERK5 and truncated ERK5 (ERK5 ΔTAD) kinase activity in HEK293 cells with IC50 values of 77 nM and 300 nM, respectively [1].