MAPK

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.

OZO-H is a GST inhibitor and a potent anticancer derivative of OZO. It releases JNK1 from the GST-JNK1 complex, induces JNK1 phosphorylation, and activates c-Jun in cancer cells.

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

Dioleyl phosphatidylserine is a phospholipid that can activate PKC-γ (Protein Kinase C-gamma) when the Ca2+ concentration is below 0.5 μM, specifically at a concentration of 100 μM.

Nek2/Hec1-IN-3 (Compound 11-28) is an inhibitor of the Hec1/Nek2 interaction. It disrupts the binding between Nek2 and Hec1 and is applicable for research in tumor diseases.

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

MBA-m1 is an MLKL inhibitor that suppresses necroptosis in Mlkl−/−NIH-3T3 cells. Additionally, MBA-m1 alleviates disease conditions in mouse models of dermatitis and abdominal aortic aneurysm induced by MLKL.

(+)-Perillyl alcohol (0.25-1 mM) inhibits cell growth in SW480 cells. At a concentration of 1 mM and a duration of 24 hours, (+)-Perillyl alcohol increases the number of cells in the G0/G1 phase and reduces the number in the S phase in SW480 cells.

HPK1-IN-41 (compound Z389) functions as an HPK1 inhibitor, exhibiting an IC50 value of 0.21 nM [1].

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

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

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>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>

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>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>

KRAS G12C inhibitor 50 is a KRAS G12C inhibitor (IC50: 46.7 nM).

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

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

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.

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

SML-10-70-1 is a Novel Active Site Inhibitor of Oncogenic K-Ras G12C.

Dorrigocin A, an analog of Migrastatin, inhibits the carboxymethyltransferase involved in Ras processing, reversing the morphology of Ras-transformed NIH/3T3 cells. Dorrigocin A holds potential for research as an anticancer and anti-arthritis agent.

SOF-436 is a KRAS inhibitor that can suppress SOS1-mediated KRAS nucleotide exchange (IC50 = 60 μM) and inhibit the interaction between KRAS and the effector protein RAF. SOF-436 is applicable to cancer research.

JAK3-IN-13: Oral JAK3 inhibitor, selective & potent. Acts on NK1, JNK2, JNK3, Tyk2. Anti-tumor. IC50: JNK3, 8 nM; Tyk2, 365 nM; JNK2, 2039 nM; NK1, 4728 nM.

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

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

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].

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>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>

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>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>

KRAS inhibitor-8 is a potent KRAS G12C inhibitor.

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>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>

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.

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

<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>

(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>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>

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

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

<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>

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

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

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>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>