MAPK

<p>ERK5-IN-5 is extracellular signal-regulated kinase 5 (ERK5) inhibitor with anticancer activity anticonvulsant activity inhibits A549 cell proliferation.</p>

<p>SU3327 (halicin) is a potent, selective and substrate-competitive inhibitor of JNK(IC50 of 0.7 μM).</p>

<p>CC-90003 is a selective inhibitor of ERK 1/2. It has antitumor activity.</p>

<p>Pepinh-TRIF TFA is a 30 aa peptide associated with the immune system that blocks TRIF signaling by interfering with TLR-TRIF interaction (TLR-TRIF interaction</p>

<p>K-Ras G12C-IN-4 是一种 KRAS G12C 共价抑制剂。</p>

<p>BI-3406 is an orally active, highly potent and selective between KRAS and Son of Sevenless 1 (SOS1) interaction inhibitor(IC50 : 6 nM),with anticancer activity.</p>

<p>ETC-206 is a selective inhibitor of MNK1 and MNK2 (IC50s: 64 nM and 86 nM).</p>

<p>PF-3644022 is a selective MK2 inhibitor, effective against TNFα (IC50: 5.2 nM, Ki: 3 nM), with anti-inflammatory properties. Also blocks MK3 and PRAK.</p>

<p>KRAS G12C inhibitor 19 is a potent KRAS G12C inhibitor that shows anti-tumor activity in cellular assays, and the family inhibits tumor growth.</p>

<p>JNK-IN-13 is a JNK inhibitor that inhibits JNK3 and JNK2 and can be used in the study of diabetes, inflammation, and neurological disorders.</p>

<p>MAP4K4-IN-3 (Compound 17) may be a viable target for antidiabetic agents, a serine/threonine protein kinase.</p>

<p>LUT014 is a B-Raf inhibitor (IC50: 11.7 nM) and developed to decrease dose-limiting acneiform lesions associated with EGFR Inhibitors treatment.</p>

<p>ARS-1630 is a mutant K-ras G12C inhibitor. It is a less active enantiomer of ARS-1620.</p>

<p>XL-281: potent oral RAF kinase inhibitor, effective on wild-type and mutants, reduces tumor growth and cell proliferation, increases apoptosis.</p>

<p>GW806742X inhibits MLKL with Kd 9.3 μM, preventing necroptosis; also targets VEGFR2.</p>

<p>INH154 is a potent Nek2 and Hec1 binding (INH) inhibitor with IC50s of 120 nM in MB468 cells and 200 nM in Hela cells for INH.</p>

<p>ERK5-IN-6 is an ERK5 kinase inhibitor with antiproliferative, anticonvulsant, and antitumor activity for the study of central nervous system related diseases.</p>

<p>(R)-Ketorolac ((+)-Ketorolac) is the R-enantiomer of Ketorolac, with potent analgesic activity.</p>

<p>HI-TOPK-032 is an effective and specific inhibitor of TOPK.</p>

<p>RMC-6236 is a potent RAS(ON)MULTI inhibitor with broad-spectrum inhibitory activity against RAS-GTP.Cost-effective and quality-assured.</p>

<p>MK2-IN-3 hydrate (MK-2 Inhibitor III) is an orally active, selective, and ATP-competitive inhibitor of MAPKAP-K2 (MK-2) (IC50 of 0.85 nM)</p>

<p>Divarasib (GDC-6036), an investigational KRAS G12C inhibitor for solid tumors, has an IC50 of &lt;0.01 μM.</p>

<p>Azelnidipine (UR-12592) is a dihydropyridine used as calcium channel blocker.</p>

<p>Dilmapimod (SB-681323) is a potent inhibitor of p38 MAPK ,it potentially suppresses inflammation in chronic obstructive pulmonary disease.</p>

<p>ACBI3 is a selective pan-KRAS degrader with anticancer activity that degrades oncogenic KRAS. ACBI3 inhibits the growth of most cancer cell lines driven by KRAS mutations.</p>

<p>Methylthiouracil (NSC-193526) is a thiourea antithyroid agent that inhibits the synthesis of thyroid hormone, and it is used to treat hyperthyroidism.</p>

<p>B-Raf IN 2, compound Ia, is a highly effective and specific inhibitor of BRAF. It exhibits significant potential for cancer research.</p>

<p>Tanzisertib (CC-930) (CC-930) is a potent inhibitor of JNK1/2/3 with IC50s of 61/7/6 nM, respectively, with potential antifibrotic activity.</p>

<p>MRTX0902 is an effective and high selective inhibitor of SOS1 with an IC50 of 46 nM and a Ki of 2 nM.</p>

<p>AX-15836 is an inhibitor of ERK5 (IC50 : 8 nM).</p>

<p>Cephradine (Anspor) is a beta-lactam, first-generation cephalosporin antibiotic with bactericidal activity.</p>

<p>Regorafénib N-oxyde M2 is an active metabolite of Regorafenib.</p>

<p>MRTX-1257: selective, irreversible KRAS G12C inhibitor; IC50 of 900 pM; 31% bioavailable in mice; 77% target engagement.</p>

<p>NEK7-IN-2 (compound 23) is a potent inhibitor of the NLRP3-NEK7 interaction. It enhances the thermal stability of NEK7 and modulates the assembly of the NLRP3 inflammasome. Additionally, NEK7-IN-2 inhibits the release of IL-1β.</p>

<p>HPK1-IN-53 (compound 3a) is the most potent inhibitor of HPK1, exhibiting an IC50 value of 48 nM.</p>

AS601245.2TFA (345987-15-7 free base) (AS601245.2TFA) is a cell-permeable Inhibitor of JNK (IC50s of 150, 220, and 70 nM for hJNK1, hJNK2, and hJNK3,

<p>BTX-6654 is a cereblon-based bifunctional SOS1 PROTAC degrader. This compound exhibits antiproliferative activity against cells with various KRAS mutations by reducing the expression of downstream signaling markers pERK and pS6.</p>

<p>Murrayafoline A is a useful organic compound for research related to life sciences. The catalog number is T124835 and the CAS number is 4532-33-6.</p>

<p>MLKL-IN-7 (compound 9) is an MLKL inhibitor that exhibits anti-necrotic activity in HT-29 cells, with an IC50 value of 148.4 nM.</p>

<p>PROTAC JNK1-targeted-1 (PA2) is a JNK1 PROTAC degrader with a DC50 of 10 nM. It effectively reduces fibronectin levels and is useful in lung fibrosis research. [Pink: JNK1 inhibitor; Black: linker; Blue: CRBN Ligand]</p>

<p>Anti-osteoporosis agent-8 (Compound 4aa) is a RANKL inhibitor, capable of preventing RANKL-induced osteoclastogenesis and osteoclast differentiation, with an IC50 of 2.41 μM. Furthermore, Anti-osteoporosis agent-8 has been shown to mitigate bone loss in an ovariectomized (OVX) mouse model.</p>

<p>Pan-KRAS-IN-10 (Compound 58) acts as an inhibitor of the human tumor mutant gene KRAS. It suppresses the proliferation of KRAS mutant cells, specifically AsPC-1 (G12D mutant) and SW480 (G12V mutant), with IC50 values of 0.7 and 0.24 nM, respectively.</p>

<p>MNK-IN-4 (compound D25) is a potent and selective MNK inhibitor used in treating acute spleen injury related to sepsis.</p>

<p>A-674563: Oral Akt inhibitor (Ki: 11 nM for Akt1), also targets PKA/Cdk2, with 10-1800x selectivity over other kinases.</p>

<p>PROTAC K-Ras Degrader-4 is a molecule designed to selectively degrade oncogenic K-Ras mutants, a novel strategy for cancer research.</p>

<p>ERK1/2 inhibitor 3, a strong ERK1/2 blocker, may aid in cancer and inflammation research.</p>

<p>KRpep-2d (TFA) is a potent inhibitor of K-Ras, effectively hindering the proliferation of K-Ras-driven cancer cells, thereby serving as a valuable asset for</p>

KRAS G12D inhibitor 20 (Compound 14) is a selective G12D KRAS inhibitor with antitumor activity.

<p>DS03090629, an orally active MEK inhibitor, functions by competitively inhibiting MEK activity in the presence of ATP. This compound demonstrates strong binding affinity to both MEK and phosphorylated MEK, with dissociation constants (Kd) of 0.11 and 0.15 nM, respectively. It has shown efficacy in suppressing the proliferation of melanoma cell lines that overexpress BRAF mutations, achieving IC50 values of 74.3 and 97.8 nM for BRAF V600E and MEK1 F53L transfected A375 cells, respectively. DS03090629 is thus considered promising for anti-melanoma therapies.</p>

<p>RP03707 is a PROTAC degrader of KRASG12D.</p>

<p>Pan-RAS-IN-5 (compound 7A) is a molecular glue that facilitates the formation of a ternary complex with cyclophilin A (CYPA) and RAS(ON) protein. This complex inhibits the binding of RAF downstream of RAS, demonstrating antitumor activity.</p>

<p>PROTACKRAS G12D degrader 2 is a peptidomimetic molecule capable of inducing the degradation of SARS-CoV-2 3-chymotrypsin-like protease (3CLPro). Designed as a PROTAC molecule, it combines a dipeptidyl 3CLPro ligand based on GC-376 with a pomalidomide moiety, linked through a piperazine-piperidine linker.</p>

<p>G12 (Ras5-17) TFA is a wild-type Ras peptide comprising amino acids 5-17 (KLVVVGAGGVGKS). It serves as a control in studies involving mutant Ras peptides, such as V12.</p>

<p>PD 198306: a MEK inhibitor with antihyperalgesic properties, reduces Streptozocin-boosted active ERK1.</p>

<p>TAT-DEF-Elk-1 is a cell-penetrating peptide Elk-1 inhibitor.</p>

<p>Olomoucine hinders Cdk2, Cdc2, CDK5, ERK1, regulates the cell cycle, and fights melanoma; IC50s: 3-25 µM.</p>

<p>Pan-KRAS degrader 4 (compound 69) is a cereblon-based PROTAC KRAS degrader exhibiting anticancer activity with a DC50 value of less than 100 nM.</p>

<p>BI-2865 is a non-covalent pan-KRAS inhibitor.Cost-effective and quality-assured.</p>

<p>R 115777 is an inhibitor of farnesyl transferase.</p>

<p>PROTAC MLKL Degrader-2, a PROTAC that targets MLKL (Mixed Lineage Kinase), incorporates the PROTAC target protein ligand, E3 ligase ligand Thalidomide, and PROTAC Linker N-Methylpiperazine. The conjugate of the E3 ubiquitin ligase ligand and Linker is Thalidomide-N-Methylpiperazine. This compound exhibits antinecroptotic activity in human cell lines and effectively degrades MLKL in the HT-29 xenograft mouse model.</p>

<p>HPK1-IN-54 (Compound 16) is a potent inhibitor of HPK1 (hematopoietic progenitor kinase 1), enhancing T cell activation and proliferation by blocking HPK1 activity to exert antitumor effects. It has an IC50 of 2.67 nM for HPK1, showing excellent selectivity over the MAP4K family (&gt;100-fold) and other selected kinases (&gt;300-fold). HPK1-IN-54 exhibits moderate in vivo clearance and reasonable oral exposure in both mice and rats. Additionally, in the CT26 mouse colon cancer model, HPK1-IN-54 demonstrates significant antitumor activity and shows a synergistic effect when combined with anti-PD-1 therapy. HPK1-IN-54 holds promise for research in the field of immunology.</p>

<p>JNK-IN-18 (compound 23b) is a potent inhibitor of JNK1, boasting an IC50 of 2 nM. It demonstrates superior efficacy when compared to its IC50 values of 125 nM for JNK2 and 98 nM for BRAF(V600E).</p>

<p>JNK3inhibitor-9 (Compound 24a) is a potent, selective JNK3 inhibitor capable of crossing the blood-brain barrier (BBB), demonstrating an IC50 value of 12 nM. It effectively inhibits GSK3α/β, which is involved in Tau phosphorylation, with IC50 values of 14 nM and 35 nM, respectively. JNK3inhibitor-9 also reduces the phosphorylation of c-Jun and APP and protects neurons from Aβ1-42 toxicity.</p>

<p>KRAS inhibitor-25 (compound 151a), a pyrido[2,3-d]pyrimidine derivative, effectively inhibits KRas G12V, KRas WT, and KRas G12R with IC50 values all below 100 nM.</p>

<p>KRAS inhibitor-24 (compound 115c), a pyrido-pyridine class KRAS inhibitor, exhibits potent activity against KRas G12V, KRas WT, and KRas G12R, with IC50 values all below 100 nM.</p>

<p>Tripalmitoyl pentapeptide is a Mitogen from E Coli lipoprotein. It also is a potent macrophage B lymphocyte activator.</p>

<p>OVA-E1 peptide, as SIINFEKL variant, triggers similar p38/JNK activation in mutant and normal thymocytes.</p>

<p>Divarasib (GDC-6036) adipate is a selective and highly potent KRAS G12C inhibitor with an impressively low IC 50 value of &lt;0.01 μM, designed for oral administration. It covalently attaches to the switch II (SW-II) pocket in KRAS G12C, irreversibly maintaining the protein in its inactive GDP-bound state [1] [2].</p>

<p>GAGGVGKSAL, a wild-type KRAS G12D 10mer peptide, serves as an immunogenic neoantigen in cancer immunotherapy research [1].</p>

<p>SP 600125, negative control is a methylated analog of SP 600125 and can be used as a negative control for SP 600125.</p>

PROTACSOS1 degrader-7 (Example 15) is a SOS1 PROTAC degrader with specific antitumor activity.

<p>SOS1-IN-11 is an effective inhibitor of SOS1 (IC50 = 30 nM).</p>

<p>Peraquinsin is a MK2 activator that can be utilized in the research of vascular or endothelial barrier disorders and functions as an antihypertensive agent [1].</p>

<p>ZZ151 is an effective and selective SOS1 PROTAC with in vivo anti-tumor efficacy against KRAS-mutant cancers. This compound induces rapid and specific degradation of SOS1 and exhibits strong anti-proliferative activity against a wide range of KRAS mutation-driven cancer cells. In murine xenograft models with KRASG12D and G12V mutations, ZZ151 demonstrates superior anticancer activity. It represents a promising lead compound for developing new chemotherapeutic agents targeting KRAS mutations.</p>

<p>Ras Inhibitory Peptide acetate, involved in cancer-related Ras signaling.</p>

<p>KRAS mutant protein inhibitor 1 is a KRAS mutant protein inhibitor for potential treatment in cancer.</p>

<p>PROTAC SOS1 degrader-3 efficiently targets and breaks down SOS1 via ubiquitin-proteasome.</p>

<p>PROTAC KRAS G12C degrader-2 (compound 432) acts as a bifunctional modulator, enhancing the hydrolysis of K-Ras protein. One end of this compound features a cereblon inhibitor of apoptosis proteins (IAP), while the other end contains a moiety that binds to KRAS [1].</p>

<p>SL0101: selective, reversible ATP-competitive RSK inhibitor, membrane-permeable, IC50=89nM, potent RSK1/2 inhibitor, Ki=1μM.</p>

<p>Cyclorasin 9A5 TFA is a cell-penetrating cyclic peptide consisting of 11 residues that inhibits the interaction between Ras and Raf proteins, with an IC50 of 120 nM.</p>

<p>PROTAC K-Ras Degrader-3 is a PROTAC degrader targeting K-Ras, exhibiting a DC50 value of ≤ 1 nM against SW620 KRAS G12D and a GI50 value of ≤ 10 nM in inhibiting the growth of SW620 3D cells. It is used in cancer research.</p>

<p>(+)-Oxanthromicin, an enantiomer of the rare Streptomyces metabolite (−)-oxanthromicin, demonstrates inhibitory activity against K-Ras plasma membrane localization in MDCK cells, exhibiting an IC50 value of 62.5 μM.</p>

<p>SW083688 is a potent and highly selective inhibitor of Thousand-And-One Kinase 2 (TAOK2) with an IC 50 value of 1.3 µmol/L.</p>

<p>PROTAC BRAF-V600E degrader-2 is a useful organic compound for research related to life sciences. The catalog number is T8744 and the CAS number is 2417296-82-1.</p>

<p>G12Si-5: covalent K-RasG12S inhibitor, Ki 26 μM, targets S-IIP domain, hinders oncogenic signaling, lowers ERK phosphorylation in mutant cells.</p>

<p>SIAIS562055, a potent cereblon-based SOS1PROTAC, exhibits a dissociation constant (Kd) of 95.9 nM. It effectively degrades SOS1 and inhibits the downstream ERK pathway. SIAIS562055 disrupts the interaction between KRASG12C or KRASG12D and SOS1, with IC50 values of 95.7 nM and 134.5 nM, respectively. This compound demonstrates strong anticancer activity.</p>

<p>HRX-0233 is a small molecule inhibitor targeting MAP2K4. In vivo, HRX-0233 effectively reduces tumors in H358 KRASG12C mutant non-small cell lung cancer (NSCLC) without significant toxicity. This compound also prevents feedback activation of receptor tyrosine kinases (RTKs) when used as a monotherapy with the KRAS inhibitor Sotorasib, leading to more sustained and comprehensive inhibition of the MAPK signaling pathway. HRX-0233 holds potential for research in AR-negative prostate cancer, lung cancer, and colon cancer.</p>

<p>Pan-KRAS Ligand 1 serves as a ligand for the target protein of PROTAC (Ligand for Target Protein for PROTAC). This compound facilitates the synthesis of PROTAC Pan-KRAS Degrader 4.</p>

<p>GADGVGKSA, a mutant KRAS G12D 9mer peptide, serves as an immunogenic neoantigen for cancer immunotherapy research [1].</p>

<p>Braftide is an allosteric inhibitor of BRAF kinase that exerts its effect by targeting the surface of BRAF kinase dimers, thereby preventing their formation. It inhibits both wild-type BRAF and oncogenic BRAFG469A, with IC50 values of 364 nM and 172 nM, respectively. When combined with the TAT sequence, Braftide can suppress the MAPK signaling pathway, inhibiting the proliferation of KRAS-mutant tumor cells, with EC50 values of 7.1 μM for HCT116 and 6.6 μM for HCT-15.</p>

KRpep-2d, a potent inhibitor of K-Ras, effectively suppresses the proliferation of cancer cells driven by K-Ras.

<p>S6 Kinase Substrate Peptide 32 is a peptide that measures the activity of kinases that phosphorylate ribosomal protein S6. It can also be used as a substrate.</p>

<p>PROTAC SOS1 degrader-5 (compound 4) serves as an effective degrader of PROTAC SOS1, exhibiting a DC50 of 13 nM. It robustly suppresses the proliferation of NCI-H358 cells, with an IC50 value of 5 nM [1].</p>

<p>MORINDONE, an anthraquinone compound, exhibits significant binding affinity towards multiple targets including β-catenin, MDM2-p53, and KRAS. It displays notable cytotoxicity and selective activity against colorectal cancer cell lines, and effectively downregulates the expression of mutated TP53 and KRAS genes.</p>

<p>4′-Demethylnobiletin, a bioactive metabolite, activates the PKA/ERK/CREB signaling pathway, enhances CRE-mediated transcription in hippocampal neurons, and</p>

<p>FAM49B (190-198) mouse represents a peptide fragment of the mitochondria-localized protein FAM49B, which is instrumental in regulating mitochondrial fission, function, and integrity, in addition to influencing tumor progression. Beyond its role in mitochondrial dynamics, FAM49B serves as a negative regulator of T cell activation by inhibiting GTPase Rac activity and affecting cytoskeleton reorganization.</p>

<p>MRTX849 analog 24, a KRAS G12C inhibitor with an alkyne for click probes, aids in studying MRTX849's functionality.</p>

<p>Deltasonamide 1 TFA: PDE6δ-KRas inhibitor, K D 203 pM, used in tumor research.</p>

<p>(S)-BAY-293 is a potent pan-KRAS inhibitor for the study of primary non-small lung and pancreatic cancers.</p>

<p>Pan-KRAS degrader 5 (compound 102) is a cereblon-based PROTAC KRAS degrader with a DC50 value less than 100 nM, exhibiting anticancer activity.</p>

<p>KRAS G12D inhibitor 17, a quinazoline-linked prolinamide, degrades mutant KRAS protein; a PROTAC.</p>

<p>MRTF-A-IN-2 (compound 16) is an inhibitor of MRTF-A. It effectively suppresses cell proliferation and induces senescence in HCC cells.</p>

<p>Tagarafdeg (CFT1946) is a PROTAC degradator targeting mutant BRAF, capable of degrading BRAF V600E, G469A, G466V mutations, anti proliferation.</p>

<p>Edaxeterkib is a potent extracellular signal- regulated kinase (ERK) inhibitor for the research of cancer.</p>

<p>MEK/RAF-IN-1 (Compound 16b) serves as an inhibitor targeting both MEK and RAF, demonstrating potent efficacy with IC 50 values reported at 28 nM for MEK1, and 3 nM for both BRAF and BRAFV600E. This compound exhibits significant antitumor capabilities, effectively curbing cell proliferation in vitro in MIA PaCa-2 (G12C KRAS), HCT116 (G13D KRAS), and C26 (G12D KRAS) cells. Furthermore, MEK/RAF-IN-1 significantly restricts tumor growth in xenograft mouse models employed in the study of colorectal cancer.</p>