MAPK

<p>KRAS G12D inhibitor 17, a quinazoline-linked prolinamide, degrades mutant KRAS protein; a PROTAC.</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>Tagarafdeg (CFT1946) is a PROTAC degradator targeting mutant BRAF, capable of degrading BRAF V600E, G469A, G466V mutations, anti proliferation.</p>

<p>p38 MAP Kinase Inhibitor Ⅵ is a potent p38 MAP Kinase inhibitor with anti-inflammatory activity.</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>MEK4 inhibitor-1 targets MEK4 enzyme in pancreatic cancer, IC50=61 nM.</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>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>

<p>(R)-5-hydroxy isoindolin-1-one is an RAS protein inhibitor with antiproliferative and antitumor properties.</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>HPK1-IN-19 is a potent inhibitor of hematopoietic progenitor kinase 1 (HPK1).</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>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>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>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>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>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>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>KRAS inhibitor-42 (compound 8) is an effective USP7 inhibitor that exhibits high affinity for GDP-bound KRASG12D, with a Ki value of 2.7 μM.</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>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>Cobimetinib R-enantiomer is the less active R-enantiomer of Cobimetinib which is a selective MEK inhibitor.</p>

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

<p>PROTAC SOS1 degrader-2 reduces pERK &amp; RAS-GTP, inhibiting tumor growth dose-dependently in vivo.</p>

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

<p>ADT-007 is a pan-RAS inhibitor with potent anticancer activity.</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>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>(+)-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.</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>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>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>Peptide (45-60) blocks Rac1 binding with TrioN, GEF-H1, Tiam1 GEFs.</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>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>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>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>Vacquinol-1 is an MKK4 activator, which rapidly and selectively induces glioma cell death.</p>

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

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

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

<p>JTP10-△-TATi TFA is a selective inhibitor of JNK2 peptide (IC50: 92 nM), exhibiting 10-fold selectivity for JNK2 over JNK1 and JNK3.</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>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>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>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>A unique collection of 365 compounds targeting MAPK signaling for drug discovery in MAPK related diseases;</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>MC 976 is a derivative of Vitamin D3.</p>

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