MAPK

<p>INH154 is a potent Nek2 and Hec1 binding (INH) inhibitor with IC50s of 120 nM in MB468 cells and 200 nM in Hela cells for INH.</p>

<p>HI-TOPK-032 is an effective and specific inhibitor of TOPK.</p>

<p>Divarasib (GDC-6036), an investigational KRAS G12C inhibitor for solid tumors, has an IC50 of &lt;0.01 μM.</p>

<p>CC-90003 is a selective inhibitor of ERK 1/2. It has antitumor activity.</p>

<p>ERK5-IN-6 is an ERK5 kinase inhibitor with antiproliferative, anticonvulsant, and antitumor activity for the study of central nervous system related diseases.</p>

<p>Cephradine (Anspor) is a beta-lactam, first-generation cephalosporin antibiotic with bactericidal activity.</p>

<p>Pepinh-TRIF TFA is a 30 aa peptide associated with the immune system that blocks TRIF signaling by interfering with TLR-TRIF interaction (TLR-TRIF interaction</p>

<p>MRTX-1257: selective, irreversible KRAS G12C inhibitor; IC50 of 900 pM; 31% bioavailable in mice; 77% target engagement.</p>

<p>AX-15836 is an inhibitor of ERK5 (IC50 : 8 nM).</p>

<p>MAP4K4-IN-3 (Compound 17) may be a viable target for antidiabetic agents, a serine/threonine protein kinase.</p>

<p>Tanzisertib (CC-930) (CC-930) is a potent inhibitor of JNK1/2/3 with IC50s of 61/7/6 nM, respectively, with potential antifibrotic activity.</p>

<p>MK2-IN-3 hydrate (MK-2 Inhibitor III) is an orally active, selective, and ATP-competitive inhibitor of MAPKAP-K2 (MK-2) (IC50 of 0.85 nM)</p>

<p>ETC-206 is a selective inhibitor of MNK1 and MNK2 (IC50s: 64 nM and 86 nM).</p>

<p>XL-281: potent oral RAF kinase inhibitor, effective on wild-type and mutants, reduces tumor growth and cell proliferation, increases apoptosis.</p>

<p>Azelnidipine (UR-12592) is a dihydropyridine used as calcium channel blocker.</p>

<p>B-Raf IN 2, compound Ia, is a highly effective and specific inhibitor of BRAF. It exhibits significant potential for cancer research.</p>

<p>K-Ras G12C-IN-4 是一种 KRAS G12C 共价抑制剂。</p>

<p>ARS-1630 is a mutant K-ras G12C inhibitor. It is a less active enantiomer of ARS-1620.</p>

<p>SU3327 (halicin) is a potent, selective and substrate-competitive inhibitor of JNK(IC50 of 0.7 μM).</p>

<p>ERK5-IN-5 is extracellular signal-regulated kinase 5 (ERK5) inhibitor with anticancer activity anticonvulsant activity inhibits A549 cell proliferation.</p>

<p>Regorafénib N-oxyde M2 is an active metabolite of Regorafenib.</p>

<p>MRTX0902 is an effective and high selective inhibitor of SOS1 with an IC50 of 46 nM and a Ki of 2 nM.</p>

<p>Methylthiouracil (NSC-193526) is a thiourea antithyroid agent that inhibits the synthesis of thyroid hormone, and it is used to treat hyperthyroidism.</p>

<p>PF-3644022 is a selective MK2 inhibitor, effective against TNFα (IC50: 5.2 nM, Ki: 3 nM), with anti-inflammatory properties. Also blocks MK3 and PRAK.</p>

<p>KRAS G12C inhibitor 19 is a potent KRAS G12C inhibitor that shows anti-tumor activity in cellular assays, and the family inhibits tumor growth.</p>

<p>Dilmapimod (SB-681323) is a potent inhibitor of p38 MAPK ,it potentially suppresses inflammation in chronic obstructive pulmonary disease.</p>

<p>JNK-IN-13 is a JNK inhibitor that inhibits JNK3 and JNK2 and can be used in the study of diabetes, inflammation, and neurological disorders.</p>

<p>GW806742X inhibits MLKL with Kd 9.3 μM, preventing necroptosis; also targets VEGFR2.</p>

<p>LUT014 is a B-Raf inhibitor (IC50: 11.7 nM) and developed to decrease dose-limiting acneiform lesions associated with EGFR Inhibitors treatment.</p>

<p>BI-3406 is an orally active, highly potent and selective between KRAS and Son of Sevenless 1 (SOS1) interaction inhibitor(IC50 : 6 nM),with anticancer activity.</p>

<p>RMC-6236 is a potent RAS(ON)MULTI inhibitor with broad-spectrum inhibitory activity against RAS-GTP.Cost-effective and quality-assured.</p>

<p>(R)-Ketorolac ((+)-Ketorolac) is the R-enantiomer of Ketorolac, with potent analgesic activity.</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>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>ERK1/2 inhibitor 3, a strong ERK1/2 blocker, may aid in cancer and inflammation research.</p>

<p>Peptide based on JIP-1(153-163) inhibits JNK with micromolar affinity; barely affects p38, ERK.</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>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>Rapaprutug is a monoclonal antibody that targets human KARS1 (lysyl-tRNA synthetase 1). It can block inflammation-related signaling pathways involving KARS1, thereby reducing the production and release of inflammatory factors. Rapaprutug shows potential for research into inflammatory diseases.</p>

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

<p>MC 976 is a derivative of Vitamin D3.</p>

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

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

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

<p>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.</p>

<p>Rutamycin: a macrolide antibiotic from Streptomyces rutgersensis; blocks ATPases, uncouples oxidative phosphorylation.</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>Rineterkib hydrochloride (B) is an oral RAF/ERK1/2 inhibitor for MAPK-driven cancers, including KRAS/BRAF-mutant NSCLC and CRC.</p>

<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>

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

<p>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>

<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.</p>

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

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

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

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

<p>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.</p>

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

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

<p>KRAS G12D inhibitor 7, is a highly potent inhibitor specifically targeting KRAS G12D.</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>SS47 is a PROTAC that degrades immunosuppressive HPK1 via proteasome; boosts BCMA CAR-T cell cancer therapy.</p>

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

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

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

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

<p>Cobimetinib R-enantiomer is the less active R-enantiomer of Cobimetinib which is a selective MEK inhibitor.</p>

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

<p>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.</p>

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

<p>Tagarafdeg (CFT1946) is a PROTAC degradator targeting mutant BRAF, capable of degrading BRAF V600E, G469A, G466V mutations, anti proliferation.</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>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>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>HPK1-IN-19 is a potent inhibitor of hematopoietic progenitor kinase 1 (HPK1).</p>

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

<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>

<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>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>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>

<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>

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

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

<p>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>

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

<p>KRAS G12D inhibitor 17, a quinazoline-linked prolinamide, degrades mutant KRAS protein; a PROTAC.</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>Inactive analog of U0126(MEK-1/2 inhibitor), used as a negative control</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>