erk in 2

ERK-IN-2, an ERK2 inhibitor, exhibits an IC50 value of 1.8 nM. At doses greater than 10 μM, it may induce off-target toxicity and or activity [1].

ERK-IN-2 free base, an inhibitor of ERK2, demonstrates potent efficacy with an IC50 value of 1.8 nM. However, doses exceeding 10 μM may result in off-target toxicity and or activity.

EF24 (3,5-Bis[(2-fluorophenyl)Methylene]-4-piperidinone) treatment increases the levels of activated caspase 3 and 9, and decreases the phosphorylated forms of MEK1 and ERK. EF24 shows potent anti-tumor activity in oral squamous cell carcinoma (OSCC) via deactivation of the MAPK ERK signaling pathway.

Imperatorin (8-Isopentenyloxypsoralene) is a modulator of p38, ERK pathway. Imperatorin increases BMP-2 expression (mRNA) and increases bone density volume and mineralization in vivo.

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

1. Oleandrin (Folinerin), the principal cardiac glycoside component of PBI-524, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels. 2. Oleandrin are known to inhibit the Na, K-ATPase pump, resulting in a consequent increase in calcium influx in heart muscle. 3. Oleandrin has stronger anti-proliferative activity in undifferentiated CaCO-2 cells (IC50, 8.25 nM) , causes an autophagic cell death and altered ERK phosphorylation in undifferentiated.

ERK2 IN-1, a selective ERK2 inhibitor, exhibits an IC50 of 7 nM.

MAPK-IN-3 (Compound 4a) is an antiproliferative agent demonstrating significant inhibitory effects on KYSE 30, HCT 116, and HGC 27 cell lines, with IC50 values of 0.57 μM, 3.27 μM, and 2.28 μM, respectively. This compound arrests the cell cycle via a p53-dependent mechanism and induces apoptosis through a p53-independent pathway. It reduces the expression of cell cycle-related proteins, such as Cyclin D1 and Cyclin B1, while increasing pro-apoptotic proteins like cleaved PARP, cleaved caspase-7, and cleaved caspase-9. MAPK-IN-3 also decreases anti-apoptotic proteins such as Bcl-2, elevates ROS levels in KYSE 30 cells, and enhances the expression of ROS-related MAPK pathway members, including p-ERK, p-p38, and p-JNK.

SOS1-IN-17 (Compound 8d) is an orally active inhibitor targeting the SOS1-KRASG12C interaction, with an IC50 of 5.1 nM. It suppresses ERK phosphorylation in DLD-1 cells with an IC50 of 18 nM and demonstrates antiproliferative activity in KRASG12C-mutant Mia-Paca-2 cells, with an IC50 of 0.11 μM. In mouse models, SOS1-IN-17 shows antitumor efficacy against pancreatic cancer.

NF-κB MAPK-IN-2 (compound 14) is a potent inhibitor of NF-κB and MAPK pathways. It effectively reduces the protein expression levels of p-p65, p-IκB, p-p38, p-JNK, and p-ERK. This compound decreases the release of TNF-α and IL-6 induced by LPS and inhibits the nuclear translocation of p65 and c-Fos. NF-κB MAPK-IN-2 shows potential for research in sepsis.

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.

KRAS G12C inhibitor 69 (Compound K09) is an inhibitor of the mutant RAS protein KRAS G12C with an IC50 of 4.36 nM. In the cell lines NCI-H358 and MIA-PACA-2, it suppresses ERK phosphorylation with IC50 values of 12 nM and 7 nM, respectively. Additionally, KRAS G12C inhibitor 69 hinders the proliferation of NCI-H358 and MIA-PACA-2 cancer cells, with IC50 values of 3.15 nM and 2.33 nM, respectively.

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.

KRASG12C IN-15 (Compound 21) is an orally active KRASG12C inhibitor that effectively blocks SOS1-mediated GDP GTP exchange with an IC50 of 19 nM. It inhibits ERK phosphorylation with an IC50 of 0.051 μM and reduces the viability of KRASG12C mutant MIA PaCa-2 cells with an IC50 of 0.023 μM. Additionally, KRASG12C IN-15 demonstrates antitumor activity in a MIA PaCa-2 xenograft mouse model.

6-Hydroxyflavone (6-HF) is a noncompetitive inhibitors of cytochrome P450 2C9. It is a flavone, a type of chemical compound. It is reported in leaves of Barleria prionitis Linn. (a common Acanthaceae from India). 6-Hydroxyflavone may have a potential as a therapeutic drug capable for the treatment of anxiety-like disorders.

PF-04856264 is a Nav1.7 blocker.Nav1.7 is a chondrocyte modulator and a therapeutic target in osteoarthritis.Inhibition of Nav1.7 modulates intracellular Ca 2+ signaling and chondrocyte secretome, raises the threshold of mechanical pain and inhibits ERK expression, which has analgesic and anti-inflammatory effects.

Darinaparsin is a dimethylated arsenic linked to glutathione. It is cytotoxic to DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5-10 µM) and patient-derived primary prostate cancer cells (IC50s = 2.5-20 µM), as well as Jurkat T cell lymphoma and L540 Hodgkin lymphoma cells (IC50s = 2.7 and 1.3 µM, respectively). [1][2] It decreases the tumor-initiating subpopulation in DU145 and PC3 cells and halts the cell cycle in the G2 M phase. Darinaparsin decreases transcription of Gli-2, a transcription factor that mediates Sonic hedgehog signaling, when used at a concentration of 1.5 but not 3 µM. It decreases SHP1 phosphatase activity and increases ERK phosphorylation. [2] Darinaparsin reduces tumor growth in DU145 and PC3 prostate cancer mouse xenograft models when administered at a dose of 100 mg kg every other day.[1]

C2 Phytoceramide is a bioactive semisynthetic sphingolipid that inhibits formyl peptide-induced oxidant release (IC50 = 0.38 μM) in suspended polymorphonuclear cells. It increases COX-2 protein levels 15-fold through ERK signaling. It induces death of keratinocytes (20% viability) with an ED50 value of 30 μM, the same concentration at which 35% of cells in a TUNEL assay are apoptotic. C2 Phytoceramide also has antiproliferative effects in CHO cells, with greater than 80% cytotoxicity achieved at a concentration of 20 μM, and induces internucleosomal DNA fragmentation. In addition, it inhibits the activation of phospholipase D (PLD) mediated by muscarinic acetylcholine receptors in vitro.

The extracellular signal-regulated kinase (ERK) signal transduction pathway regulates a diverse array of cellular processes. These processes include cell survival, proliferation, motility, and differentiation and are constitutively activated in cancers involving lung, colon, pancreas, kidney, and ovary. CAY10561 is a potent, ATP-competitive inhibitor of ERK2 (Ki = 2 nM). This compound is highly selective for ERK2 compared to other kinases such as PKA (Ki = 0.39 μM) and JNK3 (Ki = 4 μM). CAY10561 inhibits proliferation of COLO 205 cells with an IC50 value of 0.54 μM.

DMU-212 is a methylated derivative of resveratrol with antimitotic, anti-proliferative, antioxidant, and apoptosis-promoting activities. It induces mitotic arrest, apoptosis, and activation of ERK1 2 protein and has oral activity[1][2]. DMU-212 (0.3125-40 μM) inhibits the growth of human melanoma cells (A375, MeWo, Bro, M5)[1]. At concentrations of 30-50 μM over 24 hours, it upregulates cell cycle inhibitors, induces apoptosis, and activates ERK in A375 cells[1]. DMU-212 also induces G2 M arrest and apoptosis in cancer cells[1]. In a xenograft model of human ovarian cancer with six-week-old SCID female mice (20-24 g), DMU-212 (50 mg kg, administered orally three times a week for 14 days) inhibits tumor growth[2]. [1]. Vasilis Pericles Androutsopoulos, et al. Activation of ERK1 2 is required for the antimitotic activity of the resveratrol analogue 3,4,5,4'-tetramethoxystilbene (DMU-212) in human melanoma cells. Exp Dermatol. 2015 Aug;24(8):632-4. [2]. Hanna Piotrowska, et al. DMU-212 inhibits tumor growth in xenograft model of human ovarian cancer. Biomed Pharmacother. 2014 May;68(4):397-400.

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].

Jaceosidin has anti-oxidative activity. Jaceosidin has anti-inflammatory activity, also a microglial inhibitor with anti-neuroinflammation activity. aceosidin has anticancer activity, modulates the ERK ATM Chk1 2 pathway, leading to inactivation of the Cd

ERK-IN-3 benzenesulfonate is a potent and orally active inhibitor of ERK . ERK-IN-3 benzenesulfonate inhibits ERK1 2 with low single-digit nM IC 50 values. ERK-IN-3 benzenesulfonate can be used for the research of cancers driven by RAS mutations.

1. β,β-Dimethylacrylshikonin (Dimethylacrylshikonin) is a promising agent for developing an improved strategy for radiotherapy against tumors. (a) Injection of Dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. (b) Dimethylacrylshikonin significantly suppressed the growth of H(22) transplantable hepatoma, and induced the activation of caspase-3 . (c) Dimethylacrylshikonin inhibited growth of gastric cancer SGC-791 cells by inducing ERK signaling pathway. 2. Dimethylacrylshikonin inhibits the proliferation of MCF-7 cells in vitro by inducing apoptosis through the downregulation of Bcl-2, upregulation of Bax and partial inactivation of the NF-κB pathway.