erk phosphorylation

Licochalcone D may be a potential drug for human melanoma treatment by inhibiting proliferation, inducing apoptosis via the mitochondrial pathway and blocking cell migration and invasion. Licochalcone D has cardioprotective potential against myocardial is

AZD8330 (ARRY-704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM. Phase 1.

MRTX1133 is a KRAS G12D inhibitor (KD=0.2 pM) that is potent, selective, and non-covalent. MRTX1133 exhibits inhibitory activity against KRAS G12D-mutated tumors, but not against KRAS wild-type tumors.

L-161982 is a selective EP4 receptor antagonist that inhibits PGE2-induced ERK phosphorylation and cell proliferation in HCA-7 cells and alleviates collagen-induced arthritis in mice.

G12Si-5 is a covalent inhibitor of the K-RasG12S mutant with a Ki value of 26 μM. It binds to the S-IIP structural domain, inhibiting oncogenic signaling and reducing ERK phosphorylation levels in KRAS G12S mutant cells.

Urolithin B is one of the gut microbial metabolites of ellagitannins and is found in diverse plant foods, including pomegranates, berries, walnuts, tropical fruits, and medicinal herbs. Urolithin B inhibits NF-κB activity by reducing the phosphorylation and degradation of IκBα, and suppresses the phosphorylation of JNK, ERK, and Akt, and enhances the phosphorylation of AMPK. Urolithin B is also a regulator of skeletal muscle mass. Urolithin B has anti-inflammatory and antioxidant effects.

Acalabrutinib (ACP-196), also known as ACP-196, is an orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

3-Methoxytyramine (3-O-methyl Dopamine) is a cellular metabolite of dopamine (3-hydroxytyramine), a neuromodulator that induces behavioral effects, induces significant ERK and CREB phosphorylation, and is capable of inducing a complex set of aberrant involuntary movements in acutely depleted dopamine-containing mice.

MRTX-1257 is a selective, irreversible, and covalent inhibitor of KRAS G12C with an IC50 of 900 pM for KRAS-dependent ERK phosphorylation in H358 cells. MRTX-1257 demonstrated 31% bioavailability in the mouse, with free fraction exposures well above cellular potency, and 77% target engagement in a PK/PD experiment.

KRASG12C IN-14 (compound 15), a potent inhibitor specifically designed for the KRAS G12C mutation, exhibits impressive efficacy in impeding CYPA-dependent KRAS-BRAF interaction and ERK phosphorylation in NCI-H358 cells, both with an IC 50 of 0.002 μM.

Cernuumolide J (TMJ-105) functions as a JAK2/STAT3 inhibitor and exhibits potent activity against HEL leukemia cells by inhibiting their growth in both time-dependent and concentration-dependent manners, with an IC 50 value of 1.79 μM. This compound effectively induces G2/M phase arrest and apoptosis by downregulating the phosphorylation of JAK2, STAT3, and Erk, while simultaneously upregulating the phosphorylation of JNK and p38 MAPK. Cernuumolide J holds potential for research applications in anti-cancer therapy.

SJ-C1044 is an orally effective pan-RAF inhibitor demonstrating immunomodulatory and antitumor activities. It targets wild-type BRAF, wild-type CRAF, and BRAF(V600E) with IC50 values of 331, 257, and 187 nM, respectively. SJ-C1044 suppresses tumor cell proliferation by inhibiting kras activation and MEK-ERK phosphorylation. Additionally, it shows inhibition of VEGFR2, TIE2, and CSF1R, with IC50 values of 100, 23, and 235 nM respectively. The compound enhances the tumor immune microenvironment through inhibition of angiogenesis and modulation of macrophage function. SJ-C1044 is applicable for research in colorectal cancer.

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.

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 inhibitor-40 (Compound 41) is an inhibitor of KRAS, disrupting the KRAS G12C-BRAF complex and suppressing the phosphorylation of the downstream ERK signaling pathway. This compound also inhibits the proliferation of tumor cells with various KRAS mutations, exhibiting antitumor activity.

c-Fos-IN-1 (Compound P16) acts as a c-Jun inhibitor, effectively reducing the mRNA and protein levels of c-Fos. It also inhibits the phosphorylation activity of ERK and the transcriptional activity of AP-1. This compound demonstrates anticancer properties through the inhibition of the ERK/c-Fos/Jun pathway. c-Fos-IN-1 curbs the proliferation and migration of gastric cancer cells, with an IC50 of 2.31 μM for MGC-803 cells, causing cell cycle arrest at the G2/M phase and inducing apoptosis in cancer cells. Additionally, c-Fos-IN-1 hampers the growth of gastric cancer tumors.

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.

DDN is a selective Insulin Receptor activator and insulin sensitizer that mimics insulin activity with oral efficacy. It can directly bind to the receptor kinase domain, inducing Akt and ERK phosphorylation, and enhances insulin-stimulated glucose uptake. DDN significantly reduces blood glucose levels in wild-type and diabetic ob/ob and db/db mice.

KRAS inhibitor-27 (Compound 15h) is a KRAS inhibitor that effectively targets KRAS G12D/G12V mutated cells (AsPC-1 and SW620) and wild-type KRAS cells (HT-29), with IC50 values of 378 nM, 0.6 nM, and 3230 nM, respectively. It reduces ERK phosphorylation, with IC50 values of 0.6 nM and 1 nM in AsPC-1 and SW620 cells, respectively, and decreases DUSP4 expression, thereby inhibiting the MAPK signaling pathway.

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.

SOS1-IN-18 (Compound 8) is an inhibitor of the Son of Sevenless 1 protein (SOS1) with a dissociation constant (KD) of 2.6 nM. It disrupts the SOS1-KRAS G12C interaction with an IC50 of 3.4 nM, inhibits ERK phosphorylation in H358 cells with an IC50 of 31 nM, and curtails the proliferation of H358 cells with an IC50 of 5 nM.

LC-SF-14 is a selective dual inhibitor of SHP2 and FGFR, with IC50 values of 71.6 nM and 8.9 nM, respectively. It blocks FGFR2-FRS2α-SHP2-MAPK signaling and ERK phosphorylation, and also inhibits the proliferation of KATOIII cancer cells (IC50: 9.2 nM). Furthermore, LC-SF-14 exhibits antitumor activity in SNU-16 xenograft mouse models, making it suitable for research on FGFR2-driven gastric cancer.

SMU-14a is a TLR3 inhibitor with an IC50 of 0.18 µM. It suppresses IL-6 secretion in mouse peritoneal macrophages and downregulates TNF-α in human peripheral blood mononuclear cells. The compound exerts anti-inflammatory effects by reducing the phosphorylation of p65, ERK, and TBK1 via the NF-κB, MAPK, and IRF3 signaling pathways, and by lowering serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). SMU-14a is applicable in acute hepatitis research.

ZP3022 is a dual agonist targeting the glucagon-like peptide 1 receptor (GLP-1R) and cholecystokinin 2 (CCK2) receptor. It selectively enhances cAMP accumulation or ERK phosphorylation in HEK293 cells with GLP-1R or CCK2 receptor expression, compared to ERK phosphorylation in cells with the CCK1 receptor (EC50s: 0.02, 10.3, and >1,000 nM for human receptors, respectively). At 40 nM, ZP3022 promotes proliferation of rat neonatal β-cells in vitro. It also boosts glucose-induced insulin secretion (GSIS) in rat pancreatic islets at 10 and 100 nM concentrations and decreases body weight in rats at 40 nmol/kg doses twice daily. Administered at 100 nmol/kg daily, ZP3022 enhances β-cell and total pancreatic mass and improves glucose tolerance in db/db mice, while reducing food intake but not body weight in these mice.