MAPK

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

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

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.

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.

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

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>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>

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

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.

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

<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>

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>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>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>

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.

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.

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

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.

COTI-219 is an oral inhibitor of KRAS with antitumor properties [1].

BBO-8520 is a dual KRASG12C inhibitor that blocks ON and OFF states, disables effector binding, suppresses signaling, and induces tumor regression.

<p>Calderasib (MK-1084) is a selective KRAS G12C inhibitor (IC50 1.2 nM) with anticancer activity, usable as monotherapy or combined with PD-1 inhibitors</p>

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

KRAS ligand 3 (compound 1), a BTX-6654 target-binding ligand, exhibits synergistic tumor growth inhibition through its capacity to bind a KRAS inhibitor [1].

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.

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.

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

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.

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

TH-Z816 acts as a reversible inhibitor targeting the KRAS(G12D) mutation, exhibiting an IC50 of 14 µM. This compound is utilized in cancer research [1].

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).

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

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.

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).

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>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>

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.

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 .

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.

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.

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.

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.

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

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

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

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

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

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

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.

(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>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 inhibitor-8 is a potent KRAS G12C inhibitor.

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

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

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

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

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

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>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>

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

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.

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>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>

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>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>

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

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

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.

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.

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

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.

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.

<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>

(+)-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.

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

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

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

<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.

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

<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).

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>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>