MAPK

<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>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>

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

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

KRAS inhibitor-8 is a potent KRAS G12C inhibitor.

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

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

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

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

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

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.

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

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.

<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>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>

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>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>

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

Luvometinib is an inhibitor of the mitogen-activated protein kinase (MEK) with antitumor activity.

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.

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

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

<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>

<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.</p>

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

(+)-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.

<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>

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>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>

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

<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>

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>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>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>

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

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).

PS-166276 is a potent p38 inhibitor with low cytotoxicity. It exhibits an IC50 value of 28 nM against p38 kinase and an IC50 of 170 nM in the THP-1 TNFα assay.

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

<p>HPK1-IN-21 is a potent, orally active HPK1 kinase inhibitor with a Ki value of 0.8 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>

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

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

<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>

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 .

PF-03715455 is a potent p38 MAPK inhibitor, reducing TNFα in blood (IC50=1.7 nM) with selectivity for p38α, and may treat COPD.

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.

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.

(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>KRAS G12C inhibitor 15 is a potent KRAS G12C inhibitor .</p>

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].

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

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

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

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

<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>

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

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

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

<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>

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.

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>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>

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>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>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>