MAPK

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

MK2-IN-4 is a MAPKAPK2 (MK2) inhibitor (IC50: 45 nM). MK2-IN-4 can be used in cancer, inflammation and immunology studies.

KRAS ligand 5 acts as the target protein ligand for PROTACK-Ras Degrader-3, which specifically targets and degrades mutated KRAS proteins.

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

KRASG12C IN-13 (LY3499446), a potent inhibitor of KRAS G12C, shows potential in the study of advanced solid tumors, specifically non-small cell lung cancer and colorectal cancer.

MRTX849 acid, used to make PROTAC LC-2, effectively degrades KRAS G12C at 0.25-0.76 μM DC50.

<p>KRAS G12D inhibitor 16 targets KRAS G12D with IC50 of 0.7 nM and mutant form at 0.35 μM, useful in various cancer studies.</p>

Pan-KRAS degrader 1 (Compound 1) is a broad-spectrum KRAS degrader, exhibiting an inhibitory constant Ki value of 25 nM against KRASG12V as determined by surface plasmon resonance (SPR). Additionally, this compound demonstrates antitumor activity.

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

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

<p>Refametinib R enantiomer (RDEA119 R enantiomer) is an MEK inhibitor with an EC50 of 2.0-15 nM.Refametinib (R enantiomer) has anticancer activity and can be used</p>

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

LZTR1-KRAS modulator 1 is a regulator of the KRAS-LZTR1 interaction, enhancing the recruitment of the LZTR1-KRAS complex.

KRAS inhibitor-32 (compound 139A) is a KRAS inhibitor utilized in cancer research.

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.

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.

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].

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

<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>

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

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

<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>

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.

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.

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].

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

(+)-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.

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.

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

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.

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

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

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

<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>

<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>

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

<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>

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.

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

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).

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

<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>

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.

KRAS G12C inhibitor 20 is a KRAS G12C inhibitor.

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>J-104871 (UNII-6137X5QNJF) is an FTase inhibitor that inhibits tumor growth in nude mice transplanted with activated H-ras-transformed NIH3T3 cells.</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].

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

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.

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.

pan-KRAS-IN-17 (Example 34) is an inhibitor that targets multiple forms of the KRAS protein.

<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>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>

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

<p>p38-α MAPK-IN-10 (Compound 6) is an inhibitor of p38α, with an IC50 value of 4 nM.</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>KRAS G12C inhibitor 15 is a potent KRAS G12C inhibitor .</p>

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

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.

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.

<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>

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.

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

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

<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>

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

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

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.

MRTX-EX185 inhibits GDP-KRAS/G12D; IC50=90 nM on G12D. It also binds GDP-HRAS.

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.

(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.

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.

<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>

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.

<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.

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>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>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>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>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>