MAPK

4′-Demethylnobiletin, a bioactive metabolite, activates the PKA/ERK/CREB signaling pathway, enhances CRE-mediated transcription in hippocampal neurons, and

A unique collection of 2720 kinase inhibitors/regulators for high throughput screening and high content screening for drug discovery in kinase related diseases;

DS03090629, an orally active MEK inhibitor, functions by competitively inhibiting MEK activity in the presence of ATP. This compound demonstrates strong binding affinity to both MEK and phosphorylated MEK, with dissociation constants (Kd) of 0.11 and 0.15 nM, respectively. It has shown efficacy in suppressing the proliferation of melanoma cell lines that overexpress BRAF mutations, achieving IC50 values of 74.3 and 97.8 nM for BRAF V600E and MEK1 F53L transfected A375 cells, respectively. DS03090629 is thus considered promising for anti-melanoma therapies.

A unique collection of 365 compounds targeting MAPK signaling for drug discovery in MAPK related diseases;

AM-001, a non-competitive inhibitor of Epac1, effectively blocks the activation of Rap1, a downstream effector of Epac1, in cultured cells, and is commonly used in heart disease-related research.

Z16078526 promotes Ucp1, p38 MAPK, lipolysis, thermogenic genes, and mitochondrial activity in mouse brown adipocytes.

(S,R,S)-AHPC-Me-C10-Br is a chemically synthesized conjugate and ligand-linker for E3 ligase, MS432 for MEK1/2 inhibitors and a VHL E3 ligase linker.

SHP2-IN-38 is an innovative green fluorescent inhibitor targeting SHP2, exhibiting IC50 values as follows: 2.89 μM (SHP2), 8.73 μM (SHP1), 11.08 μM (PTP1B), and 33.07 μM (TCPTP). It impedes the SHP2-mediated ERK signaling pathway and inhibits MV4-11 cell proliferation in vitro with an IC50 of 7.90 μM. The excitation wavelength of SHP2-IN-38 is 360 nm, with a maximum emission wavelength of 550 nm in DMSO and 540 nm in DMF. Additionally, it demonstrates green fluorescent imaging in HeLa cells and zebrafish.

MAP4K4-IN-6 (Compound 15f) is a MAP4K4 inhibitor with an IC50 of 80 nM. It reduces the phosphorylation of c-Jun and exhibits neuroprotective effects. Additionally, MAP4K4-IN-6 enhances the vitality of motor neurons and can be utilized in the study of amyotrophic lateral sclerosis (ALS).

Klotho-derived peptide 1 (KP1 human) hydrochloride inhibits the interaction between TGF-β and TGF-β receptor 2, suppressing the activation of TGF-β-induced Smad2/3 and mitogen-activated protein kinase (MAPK). Additionally, it exhibits antifibrotic and renal protective effects in mouse models.

HSND80 (Compound 1) is an orally active MNK/p70S6K inhibitor, exhibiting a Kd value of 44 nM for MNK1 and 4 nM for MNK2. The residence time of HSND80 on MNK1 and MNK2 is 45 minutes and 58 minutes, respectively. HSND80 effectively inhibits non-small cell lung cancer (NSCLC) both in vitro and in vivo, and suppresses the growth of triple-negative breast cancer (TNBC) cells in vitro.

NecroX-2 is a cell-permeable necrosis inhibitor with antioxidant properties. NecroX-2 selectively suppresses necrotic cell death triggered by oxidative stress. NecroX-2 does not confer protection against apoptosis induced by staurosporine or etoposide but shows protective effects under conditions such as cold shock, hypoxia, and oxidative stress in vitro.

MRTX849 analog 24, a KRAS G12C inhibitor with an alkyne for click probes, aids in studying MRTX849's functionality.

PDE4-IN-26 (Compound A5) is an orally active, highly selective inhibitor of PDE4. It exhibits anti-inflammatory properties by inhibiting p38 MAPK phosphorylation. In mouse models of acute lung injury and chronic obstructive pulmonary disease, PDE4-IN-26 reduces lung inflammation, damage, and fibrosis, while promoting sputum secretion and alleviating cough. It is useful for researching lung injury-related diseases.

CC-401 is a specific inhibitor of JNK (Ki: 25-50nM).

FAM49B (190-198) mouse represents a peptide fragment of the mitochondria-localized protein FAM49B, which is instrumental in regulating mitochondrial fission, function, and integrity, in addition to influencing tumor progression. Beyond its role in mitochondrial dynamics, FAM49B serves as a negative regulator of T cell activation by inhibiting GTPase Rac activity and affecting cytoskeleton reorganization.

Pan-KRAS degrader 5 (compound 102) is a cereblon-based PROTAC KRAS degrader with a DC50 value less than 100 nM, exhibiting anticancer activity.

Rutamycin: a macrolide antibiotic from Streptomyces rutgersensis; blocks ATPases, uncouples oxidative phosphorylation.

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.

MEK1/2-IN-3 (Compound M15) is an inhibitor of MEK1, with an IC50 value of 10.29 nM. It effectively suppresses tumor cell proliferation and migration, induces apoptosis, and exhibits good liver microsomal stability. MEK1/2-IN-3 is applicable in the study of solid tumors.