MAPK

<p>HPK1-IN-14 is a potent inhibitor of HPK1. HPK1-IN-14 has potential for the study of HPK1-related diseases.</p>

<p>Pan-Raf/RTK inhibitor 1 (compound I-16) is a potent pan-Raf inhibitor with IC50 values of 3.49 nM (BRafV600E), 8.86 nM (ARaf), 5.78 nM (BRafWT), and 1.65 nM (CRaf). It exhibits antiproliferative activity against various cancer cell lines and can be utilized in cancer research.</p>

<p>SOS1-IN-10 is a potent inhibitor of SOS1 that acts on KRAS G12C-SOS1 (IC50: 13 nM).</p>

<p>KRAS G12D inhibitor 1 (example 243) is an inhibitor of KRAS G12D with an IC 50 of 0.8 nM for KRAS G12D-mediated ERK phosphorylation [1].</p>

<p>p38-α MAPK-IN-5: potent p38α inhibitor, IC50s: 0.1 nM (α), 0.2 nM (β), 944 nM (γ), 4100 nM (δ); anti-inflammatory, promising for asthma/COPD research.</p>

<p>KU004, a potent dual EGFR/HER2 inhibitor, exhibits anticancer properties. It inhibits the proliferation of human breast cancer SKBR3 cells by inducing G1 phase arrest. KU004 blocks the activation of HER2, EGFR, and the downstream Akt and Erk pathways, primarily inducing apoptosis (Apoptosis) through the extrinsic pathway. Additionally, KU004 is a novel quinazoline derivative.</p>

<p>KRAS inhibitor-27 (Compound 15h) is a KRAS inhibitor that effectively targets KRAS G12D/G12V mutated cells (AsPC-1 and SW620) and wild-type KRAS cells (HT-29), with IC50 values of 378 nM, 0.6 nM, and 3230 nM, respectively. It reduces ERK phosphorylation, with IC50 values of 0.6 nM and 1 nM in AsPC-1 and SW620 cells, respectively, and decreases DUSP4 expression, thereby inhibiting the MAPK signaling pathway.</p>

<p>p38α-MK2-IN-1 (Compound 36) is an inhibitor of the p38α-MK2 complex, with an IC50 of 5 nM. This compound exhibits significant anti-inflammatory properties and has the ability to aid in joint repair.</p>

<p>KRAS inhibitor-8 is a potent KRAS G12C inhibitor.</p>

<p>PF-03715455 is a potent p38 MAPK inhibitor, reducing TNFα in blood (IC50=1.7 nM) with selectivity for p38α, and may treat COPD.</p>

<p>RGT-018 is a potent oral SOS1 inhibitor with antitumor properties. It exerts its anticancer activity by inhibiting KRAS activation, thereby hindering cancer cell proliferation.</p>

<p>PS-166276 is a potent p38 inhibitor with low cytotoxicity. It exhibits an IC50 value of 28 nM against p38 kinase and an IC50 of 170 nM in the THP-1 TNFα assay.</p>

<p>Luvometinib is an inhibitor of the mitogen-activated protein kinase (MEK) with antitumor activity.</p>

<p>KRAS inhibitor-31 (compound 33), a potent agent targeting KRAS, exhibits K D (SPR) values of 0.019 nM for KRas G12D, 0.019 nM for KRas G12C, and 0.096 nM for KRas G12V, illustrating its efficacy across these variants.</p>

<p>KRas G12C inhibitor 2 is a compound that inhibits KRas G12C.</p>

<p>FMK-MEA is a potent and selective p90 Ribosomal S6 Kinase (RSK) inhibitor.</p>

<p>KRAS G12D inhibitor 26 (Compound 64B) is an inhibitor of KRAS G12D with an IC50 ≤ 100 nM.</p>

<p>SR-302 is a potent and selective inhibitor of DDR/p38, with IC50 values of 0.125 μM for p38α, 0.023 μM for DDR1, and 0.018 μM for DDR2. It is utilized in research related to fibrotic diseases, such as kidney and lung fibrosis, atherosclerosis, and various types of cancer.</p>

<p>(R)-STU104-d6 is a deuterium-labeled variant of (R)-STU104. This compound acts as a potent and orally active inhibitor of the interaction between TAK1 and MKK3 proteins, exhibiting IC50 values of 0.58 μM for TNF-α and 4.0 μM for MKK3 phosphorylation. By binding to MKK3, (R)-STU104 hinders TAK1's ability to phosphorylate MKK3, thereby disrupting the TAK1/MKK3/p38/MnK1/MK2/elF4E signaling pathway. It is utilized in research related to ulcerative colitis.</p>

<p>MRTX-EX185 inhibits GDP-KRAS/G12D; IC50=90 nM on G12D. It also binds GDP-HRAS.</p>

<p>KRASG12C IN-15 (Compound 21) is an orally active KRASG12C inhibitor that effectively blocks SOS1-mediated GDP/GTP exchange with an IC50 of 19 nM. It inhibits ERK phosphorylation with an IC50 of 0.051 μM and reduces the viability of KRASG12C mutant MIA PaCa-2 cells with an IC50 of 0.023 μM. Additionally, KRASG12C IN-15 demonstrates antitumor activity in a MIA PaCa-2 xenograft mouse model.</p>

<p>KRAS G12C inhibitor 37 targets a key signaling protein, showing promise for cancer research involving KRAS G12C.</p>

<p>(rel)-AR234960 is an active relative configuration of AR234960. AR234960 is a non-peptide agonist of MAS.</p>

<p>p38 MAPK-IN-6 (compound c47) is an inhibitor of p38 MAPK, exhibiting a 14% inhibition rate at a concentration of 10 μM.</p>

<p>JH295 hydrate: potent, irreversible Nek2 inhibitor (IC50 = 770 nM), selective, doesn't target Cdk1, Aurora B or Plk1.</p>

<p>JD118 is an inhibitor of JNK. It effectively suppresses the activity of JNK1 and the expression of cJun (1 - 135).</p>

<p>JNK-1-IN-5 (Compound 14) is a potent JNK1 inhibitor with sub-nanomolar efficacy. It effectively inhibits TGF-β-induced epithelial-mesenchymal transition and shows promise for research targeting JNK1 as an anti-pulmonary fibrosis agent.</p>

<p>XMU-MP-9, a bifunctional compound, targets the C2 domain of Nedd4-1 and the allosteric site of K-Ras. It enhances the interaction and induces conformational changes within the Nedd4-1/K-Ras complex. Furthermore, XMU-MP-9 facilitates the ubiquitination and degradation of various K-Ras mutants and inhibits the proliferation of cells with these mutants. This compound is useful in cancer research.</p>

<p>SOS1 activator 2 (Compound 65) is a benzothiazole derivative and an activator of SOS1. It demonstrates a high binding affinity for SOS1, with a Kd of 9 nM. By modulating the Ras-ERK signaling pathway, SOS1 activator 2 is suitable for tumor research.</p>

<p>p38 Kinase inhibitor 8 (Compound CCLXXVIII) is an orally active inhibitor targeting p38β and JNK2α2, with IC50 values of 6.3 nM and 53.6 nM, respectively. It has demonstrated anti-inflammatory effects in a rat model of collagen-induced arthritis.</p>

<p>p38α inhibitor8 (Compound 1) demonstrates inhibitory activity against p38αMAPK and CK1δ, with IC50 values of 0.21 µM and 0.202 µM, respectively.</p>

<p>p38 Kinase inhibitor 7 (Comp:XXXIX) is an inhibitor of p38α, with an IC50 value of 5.25 nM. It also effectively suppresses TNFα production in THP-1 cells, demonstrating an IC50 of 5.88 nM.</p>

<p>Coelogin is an orally effective bone-protective agent that activates ER-Erk and Akt-dependent signaling pathways, thereby stimulating osteoblast differentiation. It is utilized in osteoporosis research.</p>

<p>p38 MAP Kinase-IN-1 (Compound 4) is an inhibitor of p38, suitable for studies related to inflammation and autoimmune responses.</p>

<p>JNK-IN-19 (Compound Q8) is an inhibitor of c-Jun N-terminal kinase, utilized for the treatment and/or prevention of injuries prior to, during, or following surgery.</p>

<p>(±)-Perillaldehyde exhibits antidepressant effects in mice with stress-induced depressive-like behavior by modulating the olfactory nervous system. Additionally, it demonstrates anti-inflammatory activity by activating JNK in RAW264.7 cells and suppressing the expression of TNF-α, with an IC50 value of 171.7 μM.</p>

<p>RIPK2-IN-6 (Compound 15a) is an inhibitor of RIPK that specifically targets the phosphorylation of RIPK2, thereby suppressing the NF-κB and MAPK signaling pathways. It has demonstrated anti-inflammatory and anti-fibrotic activities in a mouse model of colitis induced by Dextran sodium sulfate.</p>

<p>Lambertellin, an effective antibiotic, acts as both a bactericide and fungicide. It exerts anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages by modulating the activation of MAPK and NF-κB signaling pathways.</p>

<p>Casein kinase1δ-IN-27 (Compound 8) is an inhibitor of casein kinase 1 (CK1), effectively inhibiting CK1α, CK1δ, CK1ε, and p38α with IC50 values of 22, 16.5, 9.41, and 14.8 nM, respectively. It also suppresses DUX4 expression, with an IC50 of 10 nM.</p>

<p>JNK-IN-21 (Compound 62) is an inhibitor of JNK-1.</p>

<p>KRAS G12C inhibitor 15 is a potent KRAS G12C inhibitor .</p>

<p>CK1δ-IN-9 (Compound 8) is an inhibitor of casein kinase 1 (CK1), specifically targeting CK1δ with an IC50 of 1.4 nM. The compound also inhibits p38α and p38β with IC50 values of 0.25 μM and 0.78 μM, respectively. CK1δ-IN-9 exhibits favorable pharmacokinetic properties, including high oral bioavailability (70%) and moderate clearance.</p>

<p>p38-α MAPK-IN-10 (Compound 6) is an inhibitor of p38α, with an IC50 value of 4 nM.</p>

<p>p38-α MAPK-IN-9 (Compound 25a) is a p38-α MAPK inhibitor with a Ki value of 0.057 nM. It effectively inhibits LPS-induced TNFα production in hPBMC cells, exhibiting an IC50 of 18 nM.</p>

<p>Casein kinase1δ-IN-31 (Compound 16) is an inhibitor of casein kinase (CK), specifically targeting CK1α, CK1δ, and p38α, with IC50 values of 196 nM, 17 nM, and 18 nM, respectively. Additionally, Casein kinase1δ-IN-31 inhibits Double Homeobox 4 (DUX4) with an IC50 of 1200 nM.</p>

<p>pan-KRAS-IN-17 (Example 34) is an inhibitor that targets multiple forms of the KRAS protein.</p>

<p>AM-001 is a non-competitive inhibitor of Epac1, preventing the activation of its downstream effector Rap1 in cultured cells. This compound is utilized in research related to cardiac diseases.</p>

<p>J-104871 (UNII-6137X5QNJF) is an FTase inhibitor that inhibits tumor growth in nude mice transplanted with activated H-ras-transformed NIH3T3 cells.</p>

<p>KRAS inhibitor-37 (compound 2) is a potent inhibitor of KRAS, exhibiting low dissociation constants (KD) with various KRAS mutations: wild type (0.004 nM), G12D (0.041 nM), G12C (0.019 nM), and G12V (0.144 nM). This compound effectively inhibits cell proliferation, demonstrating half-maximal inhibitory concentrations (IC50) ranging from &lt;2 nM to 14 nM in H358, SW620, and PANC08.13 cell lines. KRAS inhibitor-37 holds potential for cancer research applications.</p>

<p>KRAS G12C inhibitor 20 is a KRAS G12C inhibitor.</p>

<p>KRAS G12C inhibitor 56, a powerful inhibitor of SOS1 with an inhibitory concentration (IC50) of 1.6 nM, holds promise for use in cancer research.</p>

<p>p38αMAPK/CK1δ inhibitor-1 (Compound 3) exhibits inhibitory activity against p38αMAPK and CK1δ, with IC50 values of 0.185 µM and 0.089 µM, respectively.</p>

<p>EBI-1051 is a highly potent and orally efficacious inhibitor of MEK (IC50: 3.9 nM).</p>

<p>G-479, a potent MEK inhibitor and improved analogue of GDC-0623, has distributed polarity enhancing bioactivity.</p>

<p>NHTD, a KRAS-PDEδ inhibitor, exerts its function by targeting the isoprenyl binding pocket of PDEδ, which alters the cellular localization of KRAS. This modification restricts the proliferation of cancer cells with KRAS mutations and induces cell apoptosis (Apoptosis). NHTD is utilized in the study of KRAS-driven non-small cell lung cancer (NSCLC).</p>

<p>SOS2 ligand 1 (compound 2) is a selective ligand for son of sevenless 2 (SOS2), exhibiting a KD value of 4.6 µM.</p>

<p>Brimarafenib is a selective RAF dimerization inhibitor, which can inhibit BRAF and CRAF, and exhibits inhibitory effects on a variety of RAF mutations.</p>

<p>KRAS G12D inhibitor 16 targets KRAS G12D with IC50 of 0.7 nM and mutant form at 0.35 μM, useful in various cancer studies.</p>

<p>Pan-KRAS degrader 1 (Compound 1) is a broad-spectrum KRAS degrader, exhibiting an inhibitory constant Ki value of 25 nM against KRASG12V as determined by surface plasmon resonance (SPR). Additionally, this compound demonstrates antitumor activity.</p>

<p>MRTX849 acid, used to make PROTAC LC-2, effectively degrades KRAS G12C at 0.25-0.76 μM DC50.</p>

<p>KRASG12C IN-13 (LY3499446), a potent inhibitor of KRAS G12C, shows potential in the study of advanced solid tumors, specifically non-small cell lung cancer and colorectal cancer.</p>

<p>KRAS inhibitor-34 (compound 27) is a KRAS inhibitor with an IC50 of 6.4 nM and is utilized in oncological research.</p>

<p>KRAS G12C inhibitor 33 is a KRAS G12C inhibitor that can be used to study cancer.</p>

<p>KRAS G12D inhibitor 11 targets KRAS G12D in cancer research (patent WO2021108683A1, compound 52).</p>

<p>Refametinib R enantiomer (RDEA119 R enantiomer) is an MEK inhibitor with an EC50 of 2.0-15 nM.Refametinib (R enantiomer) has anticancer activity and can be used</p>

<p>10-Methoxy-canthin-6-one (Mtx-C) acts as a DNA damage inducer that embeds into DNA, promoting cell cycle arrest at the G2/M phase. This process triggers myeloid differentiation in acute myeloid leukemia cells (AML) and leukemia stem cells (LSC). Differentiation in AML and LSC cells is characterized by increased expression of myeloperoxidase, CD15, CD11b, and CD14, along with the activation of p38 MAPK. 10-Methoxy-canthin-6-one is utilized in the study of leukemia.</p>

<p>KRAS G12D inhibitor 9 targets RAS protein, key in growth, showing promise against KRAS G12D cancer.</p>

<p>LZTR1-KRAS modulator 1 is a regulator of the KRAS-LZTR1 interaction, enhancing the recruitment of the LZTR1-KRAS complex.</p>

<p>KRAS inhibitor-32 (compound 139A) is a KRAS inhibitor utilized in cancer research.</p>

<p>JNK-1-IN-4 (Compound E1) is an inhibitor of JNK, targeting JNK-1, JNK-2, and JNK-3 with IC50 values of 2.7, 19.0, and 9.0 nM, respectively. This compound inhibits the phosphorylation of c-Jun and reduces the expression of TGF-β1-induced EMT markers (such as fibronectin and α-SMA). JNK-1-IN-4 exhibits favorable pharmacokinetic properties with a bioavailability of 69%. Additionally, it demonstrates antifibrotic effects in a Bleomycin-induced mouse model of idiopathic pulmonary fibrosis.</p>

<p>KRAS ligand 5 acts as the target protein ligand for PROTACK-Ras Degrader-3, which specifically targets and degrades mutated KRAS proteins.</p>

<p>INS018 055 (TNIK&amp;amp;MAP4K4-IN-2) is a TNIK and MAP4K4 inhibitor with anti-fibrotic activity.</p>

<p>Emprumapimod, an oral p38α MAPK inhibitor, targets RPMI-8226 cells, curbs LPS-induced IL-6; IC50: 100 pM; for cardiomyopathy, acute pain.</p>

<p>NDI-101150 (NMBS-2) is an HPK1 inhibitor with antitumor activity, inhibiting BLNK phosphorylation, and used in metastatic solid tumor research.</p>

<p>Rineterkib (ERK-IN-1) is an inhibitor of RAF and ERK1/2 activating mutations in the MAPK pathway.</p>

<p>CMK, an RSK2 kinase inhibitor, shows similar potency but less chemical stability compared with FMK.</p>

<p>Ravoxertinib hydrochloride is an orally bioavailable and selective inhibitor for ERK kinase activity (IC50: 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively).</p>

<p>Omtriptolide, triptolide purified from the Chinese herb, is a water-soluble derivative prodrug.</p>

<p>MLK-IN-1 (US20140256733A1, compound 68) is a highly potent and selective inhibitor of mixed lineage kinase 3 (MLK-3). It exhibits excellent brain penetration and specifically targets MLK-3.</p>

<p>2413035-41-1 is a useful organic compound for research related to life sciences. The catalog number is T8743 and the CAS number is 2413035-41-1.</p>

<p>HPK1-IN-19 is an inhibitor of hematopoietic progenitor kinase 1 (HPK1).</p>

<p>PLX7922, a RAF inhibitor, demonstrates binding affinity with BRAF V600E and exhibits inhibitory effects on pERK in BRAF V600E cell lines, while inducing pERK activation in mutant NRAS cell lines.</p>

<p>SKLB646 is an orally active multitarget kinase inhibitor that exhibits potent suppression of several kinases. It demonstrates significant inhibitory effects on SRC and VEGFR2, with IC50 values of 0.002 μmol/L and 0.012 μmol/L, respectively. Additionally, SKLB646 shows notable inhibition of B-Raf and C-Raf, with IC50 values of 0.022 μmol/L and 0.019 μmol/L, respectively. The compound inhibits the activation of the SRC signaling pathway and blocks the MAPK signaling pathway by inhibiting Raf kinases. Furthermore, SKLB646 inhibits the proliferation, migration, and invasion of human umbilical vein endothelial cells (HUVEC), thereby suppressing tumor-induced angiogenesis. SKLB646 also displays significant anti-proliferative and anti-survival effects on triple-negative breast cancer (TNBC) cell lines.</p>

<p>WQ-C-401 is an orally active inhibitor of the platelet-derived growth factor receptor (PDGFR). It inhibits cell proliferation by blocking PDGFR auto-phosphorylation in a concentration-dependent manner, with EC50 values of 3.5 nM for PDGFRαY849 and 5.8 nM for PDGFRβY1021. Additionally, WQ-C-401 suppresses the proliferation and migration of PASMCs by inhibiting PDGF-BB-induced phosphorylation of ERK1/2, reduces collagen I synthesis, and increases α-SMA expression, thereby preventing pulmonary vascular remodeling. This compound shows promise for research in the field of pulmonary arterial hypertension.</p>

<p>IHMT-RAF-128 is a potent pan-RAF inhibitor that demonstrates robust antitumor activity in xenograft mouse tumor models without causing significant toxicity.</p>