MAPK

Pan-KRAS-IN-10 (Compound 58) acts as an inhibitor of the human tumor mutant gene KRAS. It suppresses the proliferation of KRAS mutant cells, specifically AsPC-1 (G12D mutant) and SW480 (G12V mutant), with IC50 values of 0.7 and 0.24 nM, respectively.

Murrayafoline A is a useful organic compound for research related to life sciences. The catalog number is T124835 and the CAS number is 4532-33-6.

RAS/RAS-RAF-IN-1: Potent RAS & RAS-RAF inhibitor, KD 5-15μM for CYPA, antitumor properties.

<p>SOS1-IN-11 is an effective inhibitor of SOS1 (IC50 = 30 nM).</p>

Potent, oral JNK3 inhibitor-7 crosses blood-brain barrier, IC50: 53 nM (JNK3), offers neuroprotection, potential in AD research.

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

G12Si-5: covalent K-RasG12S inhibitor, Ki 26 μM, targets S-IIP domain, hinders oncogenic signaling, lowers ERK phosphorylation in mutant cells.

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

<p>Ras Inhibitory Peptide acetate, involved in cancer-related Ras signaling.</p>

BI-2865 is a non-covalent pan-KRAS inhibitor.Cost-effective and quality-assured.

Antimicrobial agent-21 is a potent mitogen activated protein kinase inhibitor with antibacterial, anti-inflammatory and antitumor activity for the treatment of

Anti-inflammatory Agent 7 suppresses proinflammatory cytokines by hindering the NF-κB/MAPK signaling pathway in both LPS-treated RAW 264.7 cells and mice.

Inactive analog of U0126(MEK-1/2 inhibitor), used as a negative control

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

PROTAC SOS1 degrader-3 efficiently targets and breaks down SOS1 via ubiquitin-proteasome.

<p>PROTAC MLKL Degrader-2, a PROTAC that targets MLKL (Mixed Lineage Kinase), incorporates the PROTAC target protein ligand, E3 ligase ligand Thalidomide, and PROTAC Linker N-Methylpiperazine. The conjugate of the E3 ubiquitin ligase ligand and Linker is Thalidomide-N-Methylpiperazine. This compound exhibits antinecroptotic activity in human cell lines and effectively degrades MLKL in the HT-29 xenograft mouse model.</p>

SW083688 is a potent and highly selective inhibitor of Thousand-And-One Kinase 2 (TAOK2) with an IC 50 value of 1.3 µmol/L.

<p>ADT-007 is a pan-RAS inhibitor with potent anticancer activity.</p>

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

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

<p>Olomoucine hinders Cdk2, Cdc2, CDK5, ERK1, regulates the cell cycle, and fights melanoma; IC50s: 3-25 µM.</p>

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.

PROTACSOS1 degrader-7 (Example 15) is a SOS1 PROTAC degrader with specific antitumor activity.

BTX-6654 is a cereblon-based bifunctional SOS1 PROTAC degrader. This compound exhibits antiproliferative activity against cells with various KRAS mutations by reducing the expression of downstream signaling markers pERK and pS6.

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

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.

Pan-RAS-IN-7 (Compound D101) is a broad-spectrum RAS inhibitor used in the synthesis of antibody-drug conjugates (ADCs). It is also applicable in cancer research.

PROTAC K-Ras Degrader-3 is a PROTAC degrader targeting K-Ras, exhibiting a DC50 value of ≤ 1 nM against SW620 KRAS G12D and a GI50 value of ≤ 10 nM in inhibiting the growth of SW620 3D cells. It is used in cancer research.

(+)-Oxanthromicin, an enantiomer of the rare Streptomyces metabolite (−)-oxanthromicin, demonstrates inhibitory activity against K-Ras plasma membrane localization in MDCK cells, exhibiting an IC50 value of 62.5 μM.

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

KRAS G12D Inhibitor 3 TFA, exhibiting an inhibitory concentration (IC50) of less than 500 nM, is effective as an antitumor agent.

<p>Sos1, a GEF, activates ERK by converting Ras-GDP to Ras-GTP via Grb2. The PVPPR peptide inhibits this by blocking Sos1/Grb2 binding.</p>

ZZ151 is an effective and selective SOS1 PROTAC with in vivo anti-tumor efficacy against KRAS-mutant cancers. This compound induces rapid and specific degradation of SOS1 and exhibits strong anti-proliferative activity against a wide range of KRAS mutation-driven cancer cells. In murine xenograft models with KRASG12D and G12V mutations, ZZ151 demonstrates superior anticancer activity. It represents a promising lead compound for developing new chemotherapeutic agents targeting KRAS mutations.

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].

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

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

<p>MRTX1133: Selective inhibitor of KRAS G12D, effective in all protein states, targeting mutant cells.</p>

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

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.

<p>PPM-3, a selective PROTAC ERK5 degrader, exhibits a potent inhibitory concentration (IC 50) of 62.4 nM.</p>

MC 976 is a derivative of Vitamin D3.

Peptide (45-60) blocks Rac1 binding with TrioN, GEF-H1, Tiam1 GEFs.

<p>PROTAC KRAS G12C degrader-1, a cereblon-based degrader, promotes CRBN/KRAS G12C dimerization and facilitates the degradation of GFP-KRAS G12C in reporter cells</p>

KRASG12C IN-2 (compound 17) is an orally active inhibitor of KRAS G12C, which effectively suppresses tumor growth in mice [1].

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.

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.

<p>MRTF-A-IN-2 (compound 16) is an inhibitor of MRTF-A. It effectively suppresses cell proliferation and induces senescence in HCC cells.</p>

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.

(R)-5-hydroxy isoindolin-1-one is an RAS protein inhibitor with antiproliferative and antitumor properties.

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

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

Rab8a GTPase-binding stapled peptide (Kd = 12.7 μM). Cell permeable; localizes to the endomembrane system.

<p>Negative control for LC 2.</p>

<p>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.</p>

SEPT9-IN-1 (compound 8b) is a SEPT9 inhibitor with an IC50 value of 94.83 μM. It exhibits cytotoxicity against human oral squamous carcinoma cells, with an IC50 of 21 µM.

PROTAC BRAF-V600E degrader-2 is a useful organic compound for research related to life sciences. The catalog number is T8744 and the CAS number is 2417296-82-1.

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

<p>KRAS G12D inhibitor 7, is a highly potent inhibitor specifically targeting KRAS G12D.</p>

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

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

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.

KRAS G12D inhibitor 5 is a KRAS G12D inhibitor for the potential treatment of pancreatic cancer.

<p>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.</p>

PROTAC SOS1 Degrader-4 (compound 10) is a potent degrader of SOS1 and exhibits antiproliferative activity [1].

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

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

GADGVGKSA, a mutant KRAS G12D 9mer peptide, serves as an immunogenic neoantigen for cancer immunotherapy research [1].

KS-58 is a derivative of KRpep-2d. It acts as an inhibitory peptide for K-Ras(G12D), selectively binding to K-Ras. KS-58 is capable of penetrating cells and interrupts the interaction between intracellular Ras and effector proteins. It inhibits the proliferation of tumor cells and exhibits antitumor activity.

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.

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

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.

<p>MRTF-A-IN-1 (compound 14) is an inhibitor of MRTF-A. It effectively suppresses cell proliferation and induces senescence in HCC cells.</p>

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.

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.

Ibetazol is an inhibitor of importin β1 (KPNB1), which functions by binding to Cys585 of importin β1, thus preventing importin β1-mediated nuclear import with an EC50 of 6.1 µM.

<p>12-oxo PDA boosts alkaloid production in E. californica, enhances B. dioica tendril curls, and blocks JA-induced cell death in A. fru mutants.</p>

<p>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.</p>

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.

<p>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.</p>

Andrographolide derivative 31 is an anti-inflammatory that blocks NF-κB, PI3K/Akt, and ERK1/2 MAPK, and restores GSH levels to protect the liver.

HPK1-IN-19 is a potent inhibitor of hematopoietic progenitor kinase 1 (HPK1).

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

<p>HPK1-IN-8 is an allosteric, inactive, conformation-selective triazolopyrimidine ketone HPK1 inhibitor.</p>

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.

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

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

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

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.

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).

<p>KRAS G12D inhibitor 6 is an efficacious compound that effectively inhibits KRAS G12D.</p>

<p>(S)-BAY-293 is a potent pan-KRAS inhibitor for the study of primary non-small lung and pancreatic cancers.</p>

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

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.

<p>N-Acetylgalactosaminyltransferase 4 (GALNT4) is a glycosyltransferase capable of inhibiting the activation of ASK1. It functions by directly binding to ASK1, preventing N-terminal dimerization and subsequent phosphorylation. This interaction leads to significant inactivation of downstream JNK/p38 and NF-κB signaling, thereby improving the prognosis of liver surgery.</p>

Rineterkib hydrochloride (B) is an oral RAF/ERK1/2 inhibitor for MAPK-driven cancers, including KRAS/BRAF-mutant NSCLC and CRC.

Natsudaidain is a useful organic compound for research related to life sciences and the catalog number is T124974.

Potent KRAS G12D inhibitor 15 targets cancer, potential for disease research. (WO2022042630A1, compound 243)

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.

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

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