MAPK

<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>

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

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

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

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>J-104871 (UNII-6137X5QNJF) is an FTase inhibitor that inhibits tumor growth in nude mice transplanted with activated H-ras-transformed NIH3T3 cells.</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 <2 nM to 14 nM in H358, SW620, and PANC08.13 cell lines. KRAS inhibitor-37 holds potential for cancer research applications.

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

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

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>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>G-479, a potent MEK inhibitor and improved analogue of GDC-0623, has distributed polarity enhancing bioactivity.</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>Anti-osteoporosis agent-11 (compound 3k) is an anti-osteoporosis compound targeting osteoclasts. It exhibits its most prominent effect by inhibiting osteoclast differentiation, with an IC50 value of 0.36 μM. Additionally, Anti-osteoporosis agent-11 suppresses osteoclast formation, bone resorption, and the expression of osteoclast-specific genes by blocking the RANKL-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways.</p>

HPK1 ligand-Linker Conjugate 1 is a synthetic target protein ligand-linker compound used in the synthesis of PROTACs, such as PROTACHPK1 Degrader-5. PROTACHPK1 Degrader-5 is a potent and orally active HPK1 PROTAC degrader with anti-tumor activity.

ADT-1004 is an inhibitor of RAS. It can be used for research involving Ras-mediated diseases.

ABS-752 is an effective and orally active molecular glue degrader targeting GSPT1 and NEK7. It exhibits cytotoxic properties and reduces the protein expression of GSPT1, SALL4, and NEK7. ABS-752 possesses anticancer activity and shows potential for research in hepatocellular carcinoma.

MNK1ligand 1 (Compound 5) is an MNK1 ligand used in the synthesis of PROTACMNK1 degrader-1.

<p>JD123 inhibits the activity of JNK1 and the expression of cJun (1-135). It is an ATP-competitive inhibitor specific to p38-γ MAPK and has no effect on ERK1, ERK2, p38-α, p38-β, and p38-δ.</p>

ERK-IN-2, an ERK2 inhibitor, exhibits an IC50 value of 1.8 nM. At doses greater than 10 μM, it may induce off-target toxicity and/or activity [1].

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

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

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

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

<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>

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

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>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>

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

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