MAPK

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

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

<p>HPK1-IN-4 is an HPK1 (MAPK41) inhibitor with an IC 50 of 0.061 nM. HPK1-IN-4 is often used as a preclinical immunotherapy tool compound.</p>

<p>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>

<p>RM-018 inhibits active KRAS G12C &amp; G12C/Y96D, possibly beating resistance with unique traits.</p>

<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.</p>

<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>

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

<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.</p>

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

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

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

<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>

<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>

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

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

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

<p>p38 MAP Kinase Inhibitor Ⅵ is a potent p38 MAP Kinase inhibitor with anti-inflammatory activity.</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>

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

<p>KRAS G12D inhibitor 5 is a KRAS G12D inhibitor for the potential treatment of pancreatic cancer.</p>

<p>Atrovastatin-PEG3-FITC (compound S31) functions as a ligand in fluorescence anisotropy assay. Its primary role is as a KRAS-PDEδ interaction inhibitor.</p>

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

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

<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.</p>

<p>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>

<p>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>

<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.</p>

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

<p>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.</p>

<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.</p>

<p>XY-02-082 is a covalent guanosine-mimetic inhibitor targeting G12C KRAS.</p>

<p>NK7-902 is a CRBN molecular glue degrader of NEK7. It fully degrades NEK7 in human primary monocytes and whole blood, yet only partially inhibits NLRP3-dependent IL-1β production. NK7-902 results in profound and lasting degradation of NEK7, but only temporarily blocks NLRP3 inflammasome activation in non-human primates via oral administration. The compound demonstrates activity in mouse systems.</p>

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

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

<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>

<p>KRas G12R inhibitor 1 targets mutant cysteines in K-Ras, binds irreversibly, and is used in cancer research.</p>

<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.</p>

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

<p>KG5 inhibits PDGFRβ, B-Raf, FLT3, KIT, c-Raf; has anticancer and antiangiogenic effects; Kd: 520 nM (PDGFRβ), 300 nM (PDGFRα).</p>

<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>

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

<p>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.</p>

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

<p>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.</p>

<p>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>

<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>

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

<p>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.</p>