MAPK

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

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

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.

Peptide based on JIP-1(153-163) inhibits JNK with micromolar affinity; barely affects p38, ERK.

TUS-007, a non-proteasome inhibiting CANDDY, is an oral KRAS G12D/V degrader for cell-free chemical knockdown and tumor suppression.

PROTAC SOS1 degrader-2 reduces pERK & RAS-GTP, inhibiting tumor growth dose-dependently in vivo.

NG 25 is a type II kinase inhibitor targeting multiple kinases with various IC50 values and reduces colorectal cancer cell viability and tumors.

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.

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

Peraquinsin is a MK2 activator that can be utilized in the research of vascular or endothelial barrier disorders and functions as an antihypertensive agent [1].

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

HRX-0233 is a small molecule inhibitor targeting MAP2K4. In vivo, HRX-0233 effectively reduces tumors in H358 KRASG12C mutant non-small cell lung cancer (NSCLC) without significant toxicity. This compound also prevents feedback activation of receptor tyrosine kinases (RTKs) when used as a monotherapy with the KRAS inhibitor Sotorasib, leading to more sustained and comprehensive inhibition of the MAPK signaling pathway. HRX-0233 holds potential for research in AR-negative prostate cancer, lung cancer, and colon cancer.

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

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.

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.

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

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.

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.

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.

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.

p38 MAP Kinase Inhibitor Ⅵ is a potent p38 MAP Kinase inhibitor with anti-inflammatory activity.

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.

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.

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.

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

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

PROTAC K-Ras Degrader-1 is a PROTAC degrader based on the Cereblon E3 ligase ligand, capable of degrading K-Ras.

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

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

KRAS inhibitor-24 (compound 115c), a pyrido-pyridine class KRAS inhibitor, exhibits potent activity against KRas G12V, KRas WT, and KRas G12R, with IC50 values all below 100 nM.

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

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.

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.

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

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

PROTAC K-Ras Degrader-4 is a molecule designed to selectively degrade oncogenic K-Ras mutants, a novel strategy for cancer research.

RP03707 is a PROTAC degrader of KRASG12D.

Pan-KRAS Ligand 1 serves as a ligand for the target protein of PROTAC (Ligand for Target Protein for PROTAC). This compound facilitates the synthesis of PROTAC Pan-KRAS Degrader 4.

PROTAC SOS1 degrader-1: potent, DC50 98.4 nM, inhibits KRAS mutant cancer cells, low-toxic antitumor.

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

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.

JTP10-△-TATi TFA is a selective inhibitor of JNK2 peptide (IC50: 92 nM), exhibiting 10-fold selectivity for JNK2 over JNK1 and JNK3.

PROTAC MLKL Degrader-1 (Compound 36) is a selective PROTAC degrader targeting MLKL, achieving a degradation maximum (D max) over 90%.

KP-14 is a PROTAC specifically designed to target KRAS.

TAK1-IN-2 is a potent and selective TAK1 inhibitor, with an IC50> of 2 nM[1].

KRas/SOS1 inhibitor; binds KRas pocket, Kd 106-176 nM; blocks nucleotide binding; cytotoxic to KRas-driven cancers; disrupts ERK-MAPK pathway; cell-permeable.

KRAS G12C inhibitor 18 is a potent, orally active compound that inhibits KRAS G12C and exhibits anti-tumor activities.