MAPK

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

<p>KRAS G12D inhibitor 28 (Compound 1) is an inhibitor of KRAS G12D and can be utilized in cancer research.</p>

<p>MLKL-IN-1 is a covalent inhibitor of MLKL with a Kd value of 50 μM.</p>

<p>INCB159020 is an orally active inhibitor of KRAS G12D, exhibiting a KRAS G12D SPR value of 2.2 nM. It demonstrates anti-tumor activity.</p>

<p>GDC-6036-NH is a precursor of compound 17a /b, which is a RAS inhibitor that can be used in cancer research.</p>

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

<p>KRAS inhibitor-13 blocks KRAS G12C (IC50: 0.883 μM) and p-ERK in some cancer cells; promising for pancreatic, colorectal, lung cancer research.</p>

<p>KRAS G12C inhibitor 46 is a potent inhibitor of KRAS G12C.</p>

<p>HPK1-IN-42 (compound 185) is an inhibitor of HPK1, displaying potent activity with an IC50 of 0.24 nM [1].</p>

<p>AMG-548 hydrochloride: orally active, p38α inhibitor (Ki=0.5 nM), 1000x less for p38γ/δ, also blocks TNFα (IC50=3 nM) &amp; inhibits casein kinase 1 δ/ε.</p>

<p>SHR902275: potent RAF inhibitor, hits RAS mutations, oral use. cRAF IC50=1.6 nM, bRAFwt IC50=10 nM, bRAFV600E IC50=5.7 nM, hinders cell growth.</p>

<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>

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

<p>ERK1/2 inhibitor 6 - potent cancer/inflammation treatment from WO2021063335A1.</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>RSK4-IN-1 is a compound exhibiting potent inhibition of RSK4, demonstrated by an IC50 value of 9.5 nM.</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>HPK1-IN-3: Selective HPK1 inhibitor, ATP-competitive, IC50=0.25nM; boosts IL-2 in PBMCs, EC50=108nM.</p>

<p>SOS1-IN-9 is a potent inhibitor of SOS1 that acts on KRAS G12C-SOS1 (IC50: 116.5 nM).</p>

<p>KRAS inhibitor-41 is a KRAS inhibitor with an IC50 value of less than 0.01 μM for both KRAS G12D and KRAS G12V mutations. It effectively inhibits RAS mutant cell lines GP2D (KRAS-G12D) and SW620 (KRAS-G12V). KRAS inhibitor-41 is applicable for cancer research.</p>

<p>KRAS G12C inhibitor 44: potent, oral, anti-cancer; halts cell growth in MIA PaCA-2, H358; effective in vivo. IC50: MIA-0.016μM, H358-0.028μM.</p>

<p>Rho GTPase inhibitor 1 (compound 7) is a potent inhibitor of Rho GTPase. It exhibits high affinity for Cdc42, Rac1, and RhoA, with dissociation constants (KDs) of 151 μM, 352 μM, and 232 μM, respectively. Additionally, Rho GTPase inhibitor 1 reduces cell migration in glioblastoma cell lines.</p>

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

<p>MEK4 Inhibitor-2, a novel MEK4 inhibitor, demonstrates efficacy against pancreatic adenocarcinoma, exhibiting an IC50 value of 83 nM.</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>PAT-IN-1, a protein acyl transferases (PAT) inhibitor, competitively inhibits Erf2 autopalmitoylation (WO2017011518A1; compound 13) [1].</p>

<p>EBI-907 is a potent, oral B-RafV600E inhibitor with an IC50 of 4.9 nM, over 10x stronger than Vemurafenib, and effective against key cancer kinases.</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>KRAS inhibitor-21 (22b) is a KRAS G12C inhibitor (IC50&lt;0.01 μM) that can be used in cancer 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>

KRASG12D-IN-3-d3 is the deuterium labeled KRASG12D-IN-3. KRASG12D-IN-3 (compound Z1084) is a KRASG12D inhibitor with oral bioactivity that can effectively inhibit the growth of tumor cells AGS and AsPC-1, with IC50 values of 0.38 nM and 1.23 nM, respectively.

<p>L 739749 is a CAAX peptidomimetic. It is also an inhibitor of farnesyl-protein transferase.</p>

<p>LSN3074753, a derivative of LY3009120, acts as a pan-RAF and Raf dimer inhibitor. This compound exhibits inhibitory activity against tumor cells driven by either BRAF monomers or RAF dimers, particularly in the activation of the MAPK pathway, including colorectal cancers with BRAF or KRAS mutations. When combined with Cetuximab, LSN3074753 demonstrates additive and synergistic effects in colorectal cancer PDX models, especially in those harboring KRAS or BRAF mutations.</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>Fulzerasib is an orally active KRAS G12C inhibitor that covalently binds to cysteine residue on the protein, thereby inhibiting the growth of KRAS G12C mutant</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>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>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-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>SOS1-IN-6 (compound 33-P1) is a potent inhibitor of SOS1, acting on SOS1-G12D (IC50: 14.9 nM) and SOS1-G12V (IC50: 73.3 nM).</p>

<p>HPK1-IN-21 is a potent, orally active HPK1 kinase inhibitor with a Ki value of 0.8 nM.</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>Cot inhibitor-3 (Compound 33) is an effective and selective cancerosaka thyroid (COT) kinase inhibitor with an IC50 of 4 nM. It can be used to prevent limpness caused by inflammation.</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>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>MEK1/2-IN-2 is a potent, ATP-competitive MEK1/2 inhibitor that exhibits equal inhibitory effects on wild-type MEK1/2 and a group of MEK1/2 mutant cells.</p>

<p>HPK1-IN-16, a potent HPK1 inhibitor, useful for cancer research and treatment.</p>

<p>BMS-214662 is a selective farnesyl transferase inhibitor with anti-tumor activity, used in research on pancreatic cancer, head and neck cancer, and lung cancer.</p>

<p>HPK1-IN-31 inhibitor with an IC 50 value of 0.8 nM. HPK1-IN-31 has anti-tumour activity and has great potential for immunotherapy .</p>

<p>AMG-548 dihydrochloride, an oral p38α inhibitor (Ki: 0.5 nM), selectively targets p38β, γ, δ, inhibits TNFα (IC50: 3 nM), and suppresses Wnt signaling.</p>

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

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

<p>K-Ras-IN-4 (compound CP163) is an inhibitor of K-Ras.</p>

<p>ERK2 IN-1 is a selective ERK2 inhibitor with an IC50 of 7 nM.</p>

<p>HPK1-IN-30 is a potent inhibitor of HPK1. HPK1-IN-30 has potential for cancer disease research.</p>

<p>ATX inhibitor 26 is an Autotaxin (ATX) inhibitor with an IC50 of 57 nM in human plasma. It effectively inhibits cell migration and collagen gel contraction. Additionally, ATX inhibitor 26 demonstrates significant antifibrotic activity, reducing collagen deposition in a Bleomycin (BLM)-induced pulmonary fibrosis model.</p>

<p>VVD-699 is a covalent inhibitor of RAS-PI3K. It forms a covalent bond with cysteine at position 242 within the RAS-binding domain of PI3Kp110α, thereby obstructing the ability of RAS to activate PI3K. VVD-699 is capable of inhibiting the growth of tumors with RAS mutations and HER2 overexpression. It is applicable in research related to RAS mutation-associated cancers, such as those involving H358 lung cancer cells, A549 cells, and FaDu cells.</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>SHR2415: Potent, selective ERK1/2 inhibitor, oral; ERK1 IC50: 2.8 nM, ERK2 IC50: 5.9 nM; effective in Colo205 (IC50: 44.6 nM), for cancer research.</p>

MCB-22-174 is a potent agonist of Piezo1 with an EC50 value of 6.28 µM. It activates Ca2+-related extracellular signal-regulated kinase and calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII) pathways, and it promotes mesenchymal stem cell osteogenic differentiation, indicating its potential application in the study of disuse osteoporosis (OP).

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

<p>HPK1-IN-55 (compound 19) is a selective and orally active inhibitor of hematopoietic progenitor kinase 1 (HPK1) with an IC50 of less than 0.51 nM. It exhibits exceptional kinase selectivity, being over 637 times more selective for HPK1 compared to GCK kinase and over 1022 times compared to LCK. HPK1-IN-55 possesses anti-cancer properties.</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>KRAS G12C inhibitor 50 is a KRAS G12C inhibitor (IC50: 46.7 nM).</p>

<p>Pan-KRAS-IN-6 (compound 12) is a potent pan-KRAS inhibitor, with IC50 values of 9.79 nM for Kras G12D and 6.03 nM for Kras G12V.</p>

<p>KRAS G12D Inhibitor 3, a compound targeting the KRAS G12D mutation, demonstrates potent antitumor efficacy with an inhibitory concentration (IC50) of less than</p>

<p>Sosimerasib is an inhibitor of the kirsten rat sarcoma viral oncogene homolog (KRAS) and exhibits antitumor activity.</p>

<p>MRTX849 is a KRAS G12C ligand and PROTAC linker for creating potent LC-2, degrading KRAS G12C with DC50 of 0.25-0.76 μM.</p>

<p>KRAS G12D inhibitor 12 targets Ras protein for cancer research. (Patent WO2021108683A1, Compound 134)</p>

<p>INS018 055 (TNIK&amp;amp;MAP4K4-IN-2) is a TNIK and MAP4K4 inhibitor with anti-fibrotic activity.</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>Emprumapimod, an oral p38α MAPK inhibitor, targets RPMI-8226 cells, curbs LPS-induced IL-6; IC50: 100 pM; for cardiomyopathy, acute pain.</p>

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

<p>Omtriptolide, triptolide purified from the Chinese herb, is a water-soluble derivative prodrug.</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>CMK, an RSK2 kinase inhibitor, shows similar potency but less chemical stability compared with FMK.</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>HPK1-IN-19 is an inhibitor of hematopoietic progenitor kinase 1 (HPK1).</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>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>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>