Zunsemetinib (CDD-450) is an orally active and selective p38α mitogen-activated protein kinase-activated protein kinase 2 (MK2) pathway inhibitor. Zunsemetinib can be used for the research of immuno-inflammatory diseases[1].
MK2-IN-5 is a Mk2 pseudosubstrate (Ki= 8 μM). MK2-IN-5 targets the protein interaction domain in the MAPK pathway. MK2-IN-5 inhibits HSP25 and HSP27 phosphorylation[1][2][3].
CMPD1 is a selective and non-ATP-competitive p38 MAPK-mediated MK2 phosphorylation inhibitor with apparent Ki (Kiapp) of 330 nM[1][2].
MMI-0100 is a cell-permeant peptide inhibitor of mitogen activated protein kinase activated protein kinase II (MK2). MMI-0100 reduces intimal hyperplasia ex vivo and in vivo. MMI-0100 suppresses IL-6 expression without effect on IL-8 expression. MMI-0100 suppresses fibrotic processes such as vein graft disease[1].
MK2-IN-4 is a MAPKAPK2 (MK2) inhibitor with an IC50 value of 45 nM. MK2-IN-4 can be used in the research of cancer, inflammation, immunology[1].
MK2-IN-3 is a potent and selective inhibitor of MAPKAP-K2 (MK-2), with an IC50 of 8.5 nM. MK2-IN-3 shows selectivity for MK-2 over MK-3, MK-5, ERK2, MNK1, p38a (IC50s=0.21, 0.081, 3.44, 5.7, and >100 μM, respectively) and MSK1, MSK2, CDK2, JNK2, IKK2 (IC50s>200 μM). MK2-IN-3 can reduce TNFα production in both U937 cells and in vivo[1].
DB1113 (Example 24) is a bifunctional compound targeted protein degradation of kinases. DB1113 degrades ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1, MAP4K2, MAP4K3, MAP4K5, MAPK14, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1, RPS6KA3, SIK2, SIK3, STK35, TNK2, and ULK1. DB1113 can be used for research of disease or disorder mediated by aberrant kinase activity[1].
MK2-IN-1 is a potent and selecitve MAPKAPK2(MK2) inhibitor(IC50=0.11 uM) with a non-ATP competitive binding mode.IC50 value: 0.11 uM [1]Target: MAPKAPK2(MK2) inhibitorMK2-IN-1 was profiled for kinase selectivity by screening against a broad panel of 150 protein kinases at a concentration of 10 μM, and only CK1γ3 was significantly inhibited at greater than 50%. MK2-IN-1 inhibited pro-inflammatory cytokine secretion from the human THP1 acute monocytic leukemia cell line, causing dose-dependent inhibition of LPS-stimulated TNFα and IL6 secretion. MK2-IN-1 also dose dependently inhibited IL1β-stimulated matrixmetalloprotease (MMP)13 secretion from the SW1353 chondrosarcoma cell line and human primary chondrocyte cultures. Of note, given its high degree of selectivity, our data suggest that MK2-IN-1 may be an excellent pharmacologic tool for specifically exploring and validating MK2 biology [3].
CC-99677 is a potent, covalent, and irreversible inhibitor of the mitogen-activated protein (MAP) kinase-activated protein kinase-2 (MK2) pathway in both biochemical (IC50=156.3 nM) and cell based assays (EC50=89 nM). CC-99677 is extracted from patent WO2020236636, compound 1[1].
MK2-IN-1 hydrochloride is a potent and selecitve MAPKAPK2(MK2) inhibitor(IC50=0.11 uM) with a non-ATP competitive binding mode.IC50 value: 0.11 uM [1]Target: MAPKAPK2(MK2) inhibitorMK2-IN-1 was profiled for kinase selectivity by screening against a broad panel of 150 protein kinases at a concentration of 10 μM, and only CK1γ3 was significantly inhibited at greater than 50%. MK2-IN-1 inhibited pro-inflammatory cytokine secretion from the human THP1 acute monocytic leukemia cell line, causing dose-dependent inhibition of LPS-stimulated TNFα and IL6 secretion. MK2-IN-1 also dose dependently inhibited IL1β-stimulated matrixmetalloprotease (MMP)13 secretion from the SW1353 chondrosarcoma cell line and human primary chondrocyte cultures. Of note, given its high degree of selectivity, our data suggest that MK2-IN-1 may be an excellent pharmacologic tool for specifically exploring and validating MK2 biology [3].
MK-2 Inhibitor III (compound 16) is an orally active, selective, and ATP-competitive MAPKAP-K2 (MK-2) inhibitor with an IC50 of 0.85 nM, and is exceptional selectivity against MK-3 (IC50=0.21 μM), MK-5 (IC50=0.081 μM), ERK2 (IC50=3.44 μM), MNK1(IC50=5.7 μM) as well as CDK2, JNK2, IKK2, MSK1, and MSK2[1].
PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC50 of 5.2 nM and a Ki of 3 nM. PF-3644022 also inhibits MK3 and p38 regulated/activated kinase (PRAK) with IC50s of 53 nM and 5.0 nM, respectively. PF-3644022 potently inhibits TNFα production and has anti-inflammatory effect[1].
Peraquinsin is a MK2 activator. Peraquinsin can be used for the research of vascular disorder or endothelial barrier disorder. Peraquinsin also is an antihypertensive agent[1].