MAPK

PAT-IN-1, a protein acyl transferases (PAT) inhibitor, competitively inhibits Erf2 autopalmitoylation (WO2017011518A1; compound 13) [1].

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].

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

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

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

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.

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>

ERK1/2 inhibitor 6 - potent cancer/inflammation treatment from WO2021063335A1.

RSK4-IN-1 is a compound exhibiting potent inhibition of RSK4, demonstrated by an IC50 value of 9.5 nM.

KRAS G12C inhibitor 33 is a KRAS G12C inhibitor that can be used to study cancer.

HPK1-IN-3: Selective HPK1 inhibitor, ATP-competitive, IC50=0.25nM; boosts IL-2 in PBMCs, EC50=108nM.

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

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

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

AZD4625 (Compound 21) is a selective, potent, orally active, covalent and mutagenic mutant GTPaseKRASG12C inhibitor.

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

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

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>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>

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.

KRASG12C IN-12 (compound-1) acts as an inhibitor of KRASG12C. It forms a ternary complex with intracellular CYPA and the activated mutant of KRASG12C.

<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>

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>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>

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.

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.

KRAS G12D inhibitor 19 (Compound 7) is used in cancer research [1]. As a specific inhibitor of KRAS G12D, it targets and potentially suppresses this mutation, which is frequently associated with various cancers.

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.

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.

MEK4 Inhibitor-2, a novel MEK4 inhibitor, demonstrates efficacy against pancreatic adenocarcinoma, exhibiting an IC50 value of 83 nM.

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.

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.

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.

KRAS inhibitor-36 (compound Abd2) directly inhibits KRAS Q61H.

Famlasertib is a potent inhibitor of the mitogen-activated protein kinase kinase kinase kinase (MAP4K) family, capable of penetrating the brain. It exhibits an IC50 value of 0.3 nM for HGK (MAP4K4) and 23.7 nM for MLK3.

ZCL279 is a small molecule modulator (SMM) that inhibits the interaction between CDC42 and intersectin (ITSN). At lower concentrations (<10 μM), ZCL279 activates Cdc42, a cytoplasmic small GTPase in the Ras superfamily, while at higher concentrations (<10 μM) it significantly inhibits it.

<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>

K-Ras-IN-4 (compound CP163) is an inhibitor of K-Ras.

<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>

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).

HPK1-IN-21 is a potent, orally active HPK1 kinase inhibitor with a Ki value of 0.8 nM.

<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.

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.

HPK1-IN-16, a potent HPK1 inhibitor, useful for cancer research and treatment.

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).

MAP855: potent, selective, oral MEK1/2 inhibitor; IC50=3 nM, pERKEC50=5 nM; effective on wild-type/mutant MEK1/2.

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 .

G12Si-1 selectively binds and inhibits K-Ras(G12S) to block oncogenic signaling and nucleotide exchange.

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.

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.

ERK2 IN-1 is a selective ERK2 inhibitor with an IC50 of 7 nM.

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.

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].

<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>

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

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

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.

<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>

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.

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.

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

<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).

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

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).

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>

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.

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.

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

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>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>

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.

<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>

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.

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.

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

<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>

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

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.

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

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