MAPK

<p>HI-TOPK-032 is an effective and specific inhibitor of TOPK.</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>Regorafénib N-oxyde M2 is an active metabolite of Regorafenib.</p>

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

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

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

<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>

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

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

K-Ras G12C-IN-4 是一种 KRAS G12C 共价抑制剂。

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

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

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

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.

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.

Azelnidipine (UR-12592) is a dihydropyridine used as calcium channel blocker.

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

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

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

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

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

AX-15836 is an inhibitor of ERK5 (IC50 : 8 nM).

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

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

<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>A unique collection of 2720 kinase inhibitors/regulators for high throughput screening and high content screening for drug discovery in kinase related diseases;</p>

<p>ADT-007 is a pan-RAS inhibitor with potent anticancer activity.</p>

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

TAT-DEF-Elk-1 is a cell-penetrating peptide Elk-1 inhibitor.

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.

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

PROTACHPK1 Degrader-4 (compound E3) is an orally active, selective PROTACHPK1 degrader with a DC50 of 3.16 nM. It exhibits over 1000 times greater selectivity for PROTACHPK1 compared to GLK. PROTACHPK1 Degrader-4 enhances immune activation and is useful in research for colon cancer and lymphoma.

<p>N-Acetylgalactosaminyltransferase 4 (GALNT4) is a glycosyltransferase capable of inhibiting the activation of ASK1. It functions by directly binding to ASK1, preventing N-terminal dimerization and subsequent phosphorylation. This interaction leads to significant inactivation of downstream JNK/p38 and NF-κB signaling, thereby improving the prognosis of liver surgery.</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.

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,

ACBI-4 is a selective PROTAC degrader targeting the active state of GTP-loaded KRAS (KRAS(on)). It demonstrates significant antiproliferative effects and effectively degrades various KRAS mutants in cancer cells, such as KRASG12R.

PROTACHPK1 Degrader-2 (compound 3) is a PROTAC degrader of HPK1, exhibiting a DC50 of 23 nM in human PBMCs. This compound plays a crucial role in cancer research.

<p>TrkB receptor antagonist; inhibits BDNF-TrkB signaling (IC50 = 0.30 nM); alters receptor shape; may reduce anxiety in mice.</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>

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

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.

Potent, oral JNK3 inhibitor-7 crosses blood-brain barrier, IC50: 53 nM (JNK3), offers neuroprotection, potential in AD research.

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

KRas G12R inhibitor 1 targets mutant cysteines in K-Ras, binds irreversibly, and is used in cancer research.

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

<p>PROTAC PD-L1 degrader-2, an orally administered compound, targets HPK1 and boosts the efficacy of PD-L1 antibody therapy.</p>

MRT-3486 (Compound 5) is a cereblon-based molecular glue degrader for NEK7. It is suitable for research on autoinflammatory diseases.

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.

NEK7-IN-1 (Compound I-15) is an inhibitor of NIMA-related kinase 7 (NEK7) with an IC50 of less than 100 nM. It also effectively inhibits the release of IL-1β, exhibiting an IC50 of less than 50 nM.

<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>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>

YN14 is a highly potent and selective KRASG12C proteolysis targeting chimera (PROTAC) capable of forming a stable KRASG12C: YN14: VHL ternary complex with low

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>PROTAC K-Ras Degrader-4 is a molecule designed to selectively degrade oncogenic K-Ras mutants, a novel strategy for cancer research.</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>Tripalmitoyl pentapeptide is a Mitogen from E Coli lipoprotein. It also is a potent macrophage B lymphocyte activator.</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>

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

Divarasib (GDC-6036) adipate is a selective and highly potent KRAS G12C inhibitor with an impressively low IC 50 value of <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>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>

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>MRTF-A-IN-1 (compound 14) is an inhibitor of MRTF-A. It effectively suppresses cell proliferation and induces senescence in HCC cells.</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].

Antidesmone from Ajuga decumbens inhibits acute lung injury by modulating MAPK and NF-κB.

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

(R)-5-hydroxy isoindolin-1-one is an RAS protein inhibitor with antiproliferative and antitumor properties.

Debromohymenialdisine is a natural product for research related to life sciences. The catalog number is T35596 and the CAS number is 75593-17-8.

KRASG12C IN-2 (compound 17) is an orally active inhibitor of KRAS G12C, which effectively suppresses tumor growth in mice [1].

Potent KRAS G12D inhibitor 15 targets cancer, potential for disease research. (WO2022042630A1, compound 243)

Rab8a GTPase-binding stapled peptide (Kd = 12.7 μM). Cell permeable; localizes to the endomembrane system.

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.

XY-02-082 is a covalent guanosine-mimetic inhibitor targeting G12C KRAS.

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

Ibetazol is an inhibitor of importin β1 (KPNB1), which functions by binding to Cys585 of importin β1, thus preventing importin β1-mediated nuclear import with an EC50 of 6.1 µM.

NK7-902 is a CRBN molecular glue degrader of NEK7. It fully degrades NEK7 in human primary monocytes and whole blood, yet only partially inhibits NLRP3-dependent IL-1β production. NK7-902 results in profound and lasting degradation of NEK7, but only temporarily blocks NLRP3 inflammasome activation in non-human primates via oral administration. The compound demonstrates activity in mouse systems.

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

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].

PROTAC K-Ras Degrader-1 is a PROTAC degrader based on the Cereblon E3 ligase ligand, capable of degrading K-Ras.

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

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

L-JNKI-1 is a cell-permeable peptide inhibitor specific for JNK, it has been shown to effectively inhibit JNK activity in in vivo studies.

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.

SOS1-IN-17 (Compound 8d) is an orally active inhibitor targeting the SOS1-KRASG12C interaction, with an IC50 of 5.1 nM. It suppresses ERK phosphorylation in DLD-1 cells with an IC50 of 18 nM and demonstrates antiproliferative activity in KRASG12C-mutant Mia-Paca-2 cells, with an IC50 of 0.11 μM. In mouse models, SOS1-IN-17 shows antitumor efficacy against pancreatic cancer.

TUS-007, a non-proteasome inhibiting CANDDY, is an oral KRAS G12D/V degrader for cell-free chemical knockdown and tumor suppression.

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

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

14.3.3 protein antagonist, blocks binding to Raf-1/Bad/ASK1/exoenzyme S, competitive, no phosphorylation needed, KD ~80 nM.

SEPT9-IN-1 (compound 8b) is a SEPT9 inhibitor with an IC50 value of 94.83 μM. It exhibits cytotoxicity against human oral squamous carcinoma cells, with an IC50 of 21 µM.

<p>Rapaprutug is a monoclonal antibody that targets human KARS1 (lysyl-tRNA synthetase 1). It can block inflammation-related signaling pathways involving KARS1, thereby reducing the production and release of inflammatory factors. Rapaprutug shows potential for research into inflammatory diseases.</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.

SAH-SOS1A TFA inhibits SOS1/KRAS interaction, binding wild/mutant KRAS with 106-175 nM affinity and blocks ERK-MAPK signaling, reducing cancer cell viability.

KP-14 is a PROTAC specifically designed to target KRAS.

6-Thio-GTP (tetrasodium) is an inhibitor of Vav1-Rac. It can suppress TCR-induced T cell proliferation and CD28-mediated T cell survival. In a murine model of allogeneic heart transplantation, 6-Thio-GTP (tetrasodium) demonstrates immunosuppressive effects, which can prolong the survival time of heart transplants.

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