erk1/2 inhibitor 1

ERK1/2 inhibitor 1 is a potent, orally bioavailable compound that exhibits 60% inhibition at 1 nM and has an IC50 of 3.0 nM against ERK1 and ERK2, respectively.

ERK1 2 inhibitor 12 (compound 76.3) is an ERK1 2 inhibitor that suppresses ERK-mediated phosphorylation of caspase-9 and p90Rsk-1 kinases. It exhibits anticancer properties and is applicable in cancer research.

ERK1 2 inhibitor 11 (compound L6) is a dual inhibitor of ERK1 2 that promotes the accumulation of DSBs and the degradation of ERK1 2 expression. This compound decreases BCL-2 levels and induces DNA damage by inhibiting PARP and ERK1 2. Additionally, ERK1 2 inhibitor 11 activates caspase 3 to induce apoptosis.

ERK1 2 inhibitor 13 (Compound 21y) is an orally bioavailable ERK inhibitor that targets ERK1 and ERK2, with IC50 values of 91.71 nM and 97.87 nM, respectively. It effectively suppresses the proliferation of cancer cell lines MCF-7, 4T1, MDA-MB-468, and HCC1970 with IC50 values of 0.67 μM, 2.76 μM, 2.15 μM, and 1.68 μM, respectively. Additionally, it inhibits cancer cell migration, induces apoptosis and autophagy in MCF-7 cells, and demonstrates anti-tumor and anti-metastatic effects in a 4T1 xenograft mouse model.

ERK1/2 inhibitor 10 (Compound 36c) is a potent inhibitor of ERK1 and ERK2, with IC50 values of 0.11 nM and 0.08 nM, respectively. It effectively hinders the phosphorylation of downstream substrates p90RSK and c-Myc. Additionally, ERK1/2 inhibitor 10 induces apoptosis and incomplete autophagy-related cell death. This compound demonstrates significant antitumor efficacy in models of triple-negative breast cancer and colorectal cancer harboring BRAF and RAS mutations.

Yoda 1 is an agonist of the Piezo1 channel that agonizes human- and mouse-derived Piezo1 (EC50=17.1/26.6 μM). Yoda 1 is also an inhibitor of glycine transporter protein 2 (GlyT2).

1. 2,5-Dihydroxyacetophenone (Quinacetophenone) possess anti-anxiety, and neuroprotective qualities. 2. 2,5-Dihydroxyacetophenone (Quinacetophenone) reatment can induce a sustained activation of JNK, ERK1/2, and p38 MAPKs, it also can potentiate the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. 3. 2,5-Dihydroxyacetophenone (Quinacetophenone) has anti-inflammatory activity in activated macrophages, raising the possibility that this compound has a therapeutic potential for inflammatory conditions. 4. 2,5-Dihydroxyacetophenone (Quinacetophenone) is an uncompetitive inhibitor of murine tyrosinase (K(I) 0.28mm), it strongly inhibits both melanogenesis and cellular tyrosinase activity in vitro in 3-isobutyl-1-methylxanthin-stimulated B16 mouse melanoma cells or in vivo in zebrafish and mouse models.

Rineterkib (ERK-IN-1) is an inhibitor of RAF and ERK1/2 activating mutations in the MAPK pathway.

Fasudil (HA-1077) is a potent inhibitor of ROCK1, PKA, PKC, and MLCK.

FLT3 VEGFR2-IN-1 (Compound 26) is a potent inhibitor of FLT3, VEGFR2, and HDAC, exhibiting IC50 values of 14.5 nM, 3.9 nM, and 30.8 nM against FLT3, VEGFR2, and HDAC1, respectively. It effectively inhibits the phosphorylation of STAT3 and ERK1 2, as well as the proliferation of leukemia cells. FLT3 VEGFR2-IN-1 demonstrates antitumor activity and is applicable in research on acute myeloid leukemia.

BRAFV600E/JNK-IN-1 (Compound 14c) is an inhibitor of JNK1, JNK2, JNK3, and BRAFV600E, with IC50 values of 0.51 μM, 0.53 μM, 1.02 μM, and 0.009 μM, respectively. It also inhibits the phosphorylation of MEK1/2 and ERK1/2. Additionally, BRAFV600E/JNK-IN-1 suppresses tumor cell proliferation, NO release, and PGE2 production, exhibiting both antitumor and anti-inflammatory activities.

Cantharidic acid is a selective inhibitor of protein phosphatase 2 (PP2A) and protein phosphatase 1 (PP1). It impedes cell viability by upregulating the ERK1/2, p38, and JNK1/2 pathways, causes cell cycle arrest at the sub-G1 phase, and induces apoptosis in NPC-39 and HONE-1 cells.

SCH772984 HCl is a selective inhibitor of ERK1 2 that displays behaviors of both type I and type II kinase inhibitors, with IC50s of 4 and 1 nM, respectively. SCH772984 HCl has nanomolar cellular potency in tumor cells with mutations in BRAF, NRAS, or KRA

PHPS1 is an inhibitor of Shp2. PHPS1 efficiently inhibits activation of Erk1/2 by the leukemia-associated Shp2 mutant, Shp2-E76K, and blocks the anchorage-independent growth of a variety of human tumor cell lines.

Rineterkib hydrochloride (compound B) is an orally active RAF and ERK1/2 inhibitor used in treating proliferative diseases characterized by activating mutations in the MAPK pathway, particularly KRAS-mutant NSCLC, BRAF-mutant NSCLC, KRAS-mutant pancreatic cancer, KRAS-mutant colorectal cancer (CRC), and KRAS-mutant ovarian cancer[1].

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 μM), showing no effect on PAR-2, PAR-3, or PAR-4. It inhibits the aggregation of human platelets induced by SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), with high selectivity relative to U46619. RWJ-56110 dihydrochloride also blocks angiogenesis and the formation of new vessels in vivo, and induces cell apoptosis[1][2].

4-CPPC is an inhibitor of macrophage migration inhibitory factor-2 (MIF-2; IC50= 27 μM).1It is selective for MIF-2 over MIF-1 (IC50= 450 μM). It inhibits MIF-2, but not MIF-1, binding to CD74in vitrowhen used at a concentration of 10 μM. 4-CPPC (5, 10, and 25 μM) inhibits MIF-2-induced ERK1/2 phosphorylation in primary human skin fibroblasts. 1.Tilstam, P.V., Pantouris, G., Corman, M., et al.A selective small-molecule inhibitor of macrophage migration inhibitory factor-2 (MIF-2), a MIF cytokine superfamily member, inhibits MIF-2 biological activityJ. Biol. Chem.294(49)18522-18531(2019)

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)

Temuterkib (LY3214996) is a potent and selective, orally available inhibitor of the extracellular signal-regulated kinase (ERK) 1 and 2, with potential antineoplastic activity.

BAY 61-3606 (Syk inhibitor IV) is a potent, ATP-competitive, reversible, and highly selective inhibitor of Syk tyrosine kinase activity (Ki= 7.5 nM), exhibiting no inhibitory effect against Btk, Fyn, Itk, Lyn, and Src.

BAY 61-3606 dihydrochloride (BAY 61-3606) is a potent and selective inhibitor of Syk kinase (Ki = 7.5 nM).

NSC-87877 disodium (NSC87877) is a cell-permeable inhibitor of both SHP-1 and SHP-2 with IC50 values of 355 and 318 nM respectively. It also inhibits EGF-induced Erk1/2 activation in HEK293 cells and significantly reduces MDA-MB-468 cell viability/proliferation.

ADA-07 is a TOPK inhibitor which interacts with TOPK at the ATP-binding pocket and inhibits its kinase activity, thereby suppressing SUV-induced phosphorylation of ERK1 2, p38, and JNKs, and subsequently inhibiting AP-1 activity.

1. Corynoxeine is a potent ERK1/2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty.