MAPK

Tagarafdeg (CFT1946) is a PROTAC degradator targeting mutant BRAF, capable of degrading BRAF V600E, G469A, G466V mutations, anti proliferation.

DB-10 serves as a precursor to 3-nbutylphthalide (NBP). It is absorbed by cells in a temperature and energy-dependent manner through the pyrilamine cation transporter. DB-10 enhances cell survival and rapidly converts into an active form in vivo, increasing accumulation within the brain. This compound is applicable in ischemic stroke research.

MEK/RAF-IN-1 (Compound 16b) serves as an inhibitor targeting both MEK and RAF, demonstrating potent efficacy with IC 50 values reported at 28 nM for MEK1, and 3 nM for both BRAF and BRAFV600E. This compound exhibits significant antitumor capabilities, effectively curbing cell proliferation in vitro in MIA PaCa-2 (G12C KRAS), HCT116 (G13D KRAS), and C26 (G12D KRAS) cells. Furthermore, MEK/RAF-IN-1 significantly restricts tumor growth in xenograft mouse models employed in the study of colorectal cancer.

RM-018 inhibits active KRAS G12C & G12C/Y96D, possibly beating resistance with unique traits.

L-JNKI-1 is a cell-permeable peptide inhibitor specific for JNK, it has been shown to effectively inhibit JNK activity in in vivo studies.

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

GNE-9815 (3-(2-cyanopropan-2-yl)-N-[2-fluoro-4-methyl-5-(7-methyl-8-oxo-7,8-dihydropyrido[2,3-d]pyridazin-3-yl)phenyl]benzamide) is a high kinase-selective

SS47 is a PROTAC that degrades immunosuppressive HPK1 via proteasome; boosts BCMA CAR-T cell cancer therapy.

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

Debromohymenialdisine is a natural product for research related to life sciences. The catalog number is T35596 and the CAS number is 75593-17-8.

S6 Kinase Substrate Peptide 32 is a peptide that measures the activity of kinases that phosphorylate ribosomal protein S6. It can also be used as a substrate.

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).

Mitogen-activated protein kinase 1 (MAPK1) activates the p38/NF-κB pathway and regulates cellular processes in sepsis-associated diseases.

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.

ERK1/2 inhibitor 3, a strong ERK1/2 blocker, may aid in cancer and inflammation research.

KRAS G12D inhibitor 7, is a highly potent inhibitor specifically targeting KRAS G12D.

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.

Cobimetinib R-enantiomer is the less active R-enantiomer of Cobimetinib which is a selective MEK inhibitor.

SIAIS562055, a potent cereblon-based SOS1PROTAC, exhibits a dissociation constant (Kd) of 95.9 nM. It effectively degrades SOS1 and inhibits the downstream ERK pathway. SIAIS562055 disrupts the interaction between KRASG12C or KRASG12D and SOS1, with IC50 values of 95.7 nM and 134.5 nM, respectively. This compound demonstrates strong anticancer activity.

IPS-06061 is an orally active molecular glue that forms a ternary complex with CRBN and KRASG12D, capable of degrading KRAS G12D, with a DC50 of less than 500 nM.

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

Vacquinol-1 is an MKK4 activator, which rapidly and selectively induces glioma cell death.

HPK1-IN-39 (Compound 10n), a selective inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) with an inhibitory concentration (IC50) of 29 nM, impedes the

LYMTAC-2 is a lysosome-targeting chimera (LYMTAC) developed to degrade membrane-associated proteins through lysosomal membrane proteins (LMP) such as RNF152, LAPTM4a, and LAPTM5. It forms a ternary complex with target proteins like KRASG12D, facilitating their relocation to lysosomes and resulting in ubiquitin-dependent degradation. This compound has potential for studying membrane protein regulation and devising strategies to counter resistance in KRAS-driven signaling pathways.

BAS 00489700 is a N-UTR interaction inhibitor. BAS 00489700 inhibits virus replication in cell culture.

PROTAC MEK1 Degrader-1, a targeted protein degradation agent, combines a MEK1 inhibitor with a von Hippel-Lindau ligand to effectively inhibit ERK1/2

YN14 is a highly potent and selective KRASG12C proteolysis targeting chimera (PROTAC) capable of forming a stable KRASG12C: YN14: VHL ternary complex with low

ADT-007 is a pan-RAS inhibitor with potent anticancer activity.

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.

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.

NUCC-0200808 (Compound 12g) is an MNK1 inhibitor with an IC50 of 42 nM. It reduces eIF4E phosphorylation and cell viability in AML cells and induces apoptosis. NUCC-0200808 shows potential for research in the field of leukemia.

HPK1-IN-8 is an allosteric, inactive, conformation-selective triazolopyrimidine ketone HPK1 inhibitor.

RTIL 13 inhibits dynamin GTPase (IC50: 2.3 μM), targets its lipid binding domain, and suppresses endocytosis (IC50: 9.3 & 7.1 μM).

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.

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.

BI1701963 is an orally effective inhibitor that targets the SOS1 and KRAS interaction, specifically inhibiting the activation of KRAS by blocking its GTP loading. This compound is utilized in cancer research to explore potential therapeutic effects against KRAS-driven malignancies.

KRAS Inhibitor-38 (Example 18) is a potent inhibitor capable of effectively suppressing the activity of KRAS G12C, KRAS G12D, and KRAS G12V in vivo.

KRAS G12D inhibitor 17, a quinazoline-linked prolinamide, degrades mutant KRAS protein; a PROTAC.

MC 976 is a derivative of Vitamin D3.

Pan-RAS-IN-6 (compound 24) serves as a DUSP6 inhibitor, effectively reducing MAPK activation in the NCI-H1373-Luc model (DUSP6). It concurrently exhibits notable tumor growth inhibition and regression in the NSCLC brain metastasis mouse model. The compound displays high selectivity and potent inhibitory effects, particularly on KRAS mutation-associated signaling pathways. It demonstrates varied inhibitory activities against distinct KRAS mutants and their interacting proteins. The IC 50 values for KRAS G12C, G12D, and G12V are 1.3 nM, 4.7 nM, and 0.3 nM, respectively.

PROTAC K-Ras degrader-2 (compound 48) is a broad-spectrum KRAS mutant PROTAC degrader that demonstrates an IC50 of ≤200 nM for KRAS G12V/RAF1. Additionally, PROTAC K-Ras degrader-2 achieves a DC50 of ≤200 nM in degrading SW620 KRAS G12D and inhibits the growth of SW620 3D cells with an IC50 of ≤20 nM.

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.

KRAS inhibitor-33 (compound 115a) is a pyrido[2,3-d]pyrimidine derivative that serves as an effective inhibitor of KRAS, exhibiting an IC50 value of ≤ 100nM.

14.3.3 protein antagonist, blocks binding to Raf-1/Bad/ASK1/exoenzyme S, competitive, no phosphorylation needed, KD ~80 nM.

KRAS G12C Inhibitor 60 (compound 23), a selective inhibitor targeting the Kras-G12C mutation, is utilized in the investigation of lung, colorectal, and

JNK3 inhibitor-8: potent, selective, oral, BBB-penetrating, IC50: JNK3=21 nM, JNK2=2203 nM, JNK1>10,000 nM; potential in Alzheimer's research.

KRAS G12D inhibitor 6 is an efficacious compound that effectively inhibits KRAS G12D.