MAPK

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

RM-018 inhibits active KRAS G12C & G12C/Y96D, possibly beating resistance with unique traits.

KRas/SOS1 inhibitor; binds KRas pocket, Kd 106-176 nM; blocks nucleotide binding; cytotoxic to KRas-driven cancers; disrupts ERK-MAPK pathway; cell-permeable.

<p>PPM-3, a selective PROTAC ERK5 degrader, exhibits a potent inhibitory concentration (IC 50) of 62.4 nM.</p>

<p>MHJ-627, a potent inhibitor of ERK5 (MAPK7) with an IC50 value of 0.91 μM, enhances the mRNA expression of tumor suppressors and anti-metastatic genes, leading</p>

JNK-IN-14 is a potent inhibitor of JNK with IC50 values of 1.81 nM for JNK1, 12.7 nM for JNK2, and 10.5 nM for JNK3.

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.

TAK1-IN-2 is a potent and selective TAK1 inhibitor, with an IC50> of 2 nM[1].

Pan-RAS-IN-6 (compound 24) serves as a DUSP6 inhibitor, effectively reducing MAPK activation in the NCI-H1373-Luc model (DUSP6). It concurrently exhibits notable tumor growth inhibition and regression in the NSCLC brain metastasis mouse model. The compound displays high selectivity and potent inhibitory effects, particularly on KRAS mutation-associated signaling pathways. It demonstrates varied inhibitory activities against distinct KRAS mutants and their interacting proteins. The IC 50 values for KRAS G12C, G12D, and G12V are 1.3 nM, 4.7 nM, and 0.3 nM, respectively.

KRAS inhibitor-42 (compound 8) is an effective USP7 inhibitor that exhibits high affinity for GDP-bound KRASG12D, with a Ki value of 2.7 μM.

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.

<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>

NUCC-0200808 (Compound 12g) is an MNK1 inhibitor with an IC50 of 42 nM. It reduces eIF4E phosphorylation and cell viability in AML cells and induces apoptosis. NUCC-0200808 shows potential for research in the field of leukemia.

<p>CC-401 is a specific inhibitor of JNK (Ki: 25-50nM).</p>

JTP10-△-TATi TFA is a selective inhibitor of JNK2 peptide (IC50: 92 nM), exhibiting 10-fold selectivity for JNK2 over JNK1 and JNK3.

KRASG12D-IN-6 is a PROTAC target protein ligand used in the synthesis of CH091138. CH091138 is a potent and selective KRASG12D PROTAC degrader with anti-tumor activity.

KRAS inhibitor-33 (compound 115a) is a pyrido[2,3-d]pyrimidine derivative that serves as an effective inhibitor of KRAS, exhibiting an IC50 value of ≤ 100nM.

PROTAC MEK1 Degrader-1, a targeted protein degradation agent, combines a MEK1 inhibitor with a von Hippel-Lindau ligand to effectively inhibit ERK1/2

<p>HPK1-IN-39 (Compound 10n), a selective inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) with an inhibitory concentration (IC50) of 29 nM, impedes the</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

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

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.

HPK1-IN-47, a PROTAC HPK1 degrader (DC 50: 23 nM in PBMCs), serves as a precursor for the synthesis of compounds like PROTAC HPK1 Degrader-2. It is utilized in research focused on diseases mediated by HPK1, including cancer.

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

<p>4′-Demethylnobiletin, a bioactive metabolite, activates the PKA/ERK/CREB signaling pathway, enhances CRE-mediated transcription in hippocampal neurons, and</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>PROTAC PD-L1 degrader-2, an orally administered compound, targets HPK1 and boosts the efficacy of PD-L1 antibody therapy.</p>

KRAS G12D Inhibitor 3 TFA, exhibiting an inhibitory concentration (IC50) of less than 500 nM, is effective as an antitumor agent.

Cobimetinib R-enantiomer is the less active R-enantiomer of Cobimetinib which is a selective MEK inhibitor.

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

Halociline, a derivative of alkaloids that can be isolated from the marine fungus Penicillium griseofulvum, targets MAPK1, MMP-9, and PIK3CA in gastric cancer cells. This action is potentially mediated by diverse pathways, including cancer, lipid metabolism, atherosclerosis, and EGFR tyrosine kinase inhibitor resistance. Halociline possesses antimicrobial, antioxidant, and biofilm inhibitory activities [1] [2].

HPK1 ligand 3 is a PROTAC target protein ligand (ligand for target protein for PROTAC) used in the synthesis of PROTAC HPK1 Degrader-4.

<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>

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

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.

PROTAC SOS1 Degrader-4 (compound 10) is a potent degrader of SOS1 and exhibits antiproliferative activity [1].

Vacquinol-1 is an MKK4 activator, which rapidly and selectively induces glioma cell death.

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

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

RTIL 13 inhibits dynamin GTPase (IC50: 2.3 μM), targets its lipid binding domain, and suppresses endocytosis (IC50: 9.3 & 7.1 μM).

MK2-IN-6 (Compound 11) is an effective and selective irreversible inhibitor of MK2 with an IC50 value of 2.3 nM. It suppresses the kinase activity of MK2, leading to sustained inhibition of MK2 signaling and reduction of pathological inflammatory factors in macrophages. MK2-IN-6 is capable of inhibiting the M2-like protein phenotype in macrophages both in vitro and in vivo, showing potential for use in colorectal cancer research.

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.

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.

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

<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>

VUBI1-octanoic acid is a conjugate of both the SOS1 ligand and linker, and it is applied in the synthesis of (4S)-PROTAC SOS1 degrader-1.

<p>KRAS G12D inhibitor 7, is a highly potent inhibitor specifically targeting KRAS G12D.</p>

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

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.

<p>Z16078526 promotes Ucp1, p38 MAPK, lipolysis, thermogenic genes, and mitochondrial activity in mouse brown adipocytes.</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.

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

HSND80 (Compound 1) is an orally active MNK/p70S6K inhibitor, exhibiting a Kd value of 44 nM for MNK1 and 4 nM for MNK2. The residence time of HSND80 on MNK1 and MNK2 is 45 minutes and 58 minutes, respectively. HSND80 effectively inhibits non-small cell lung cancer (NSCLC) both in vitro and in vivo, and suppresses the growth of triple-negative breast cancer (TNBC) cells in vitro.

Goralatide, isolated from fetal calf bone marrow, exerts a high inhibitory activity on the proliferation of hematopoietic pluripotent stem cells.

Rutamycin: a macrolide antibiotic from Streptomyces rutgersensis; blocks ATPases, uncouples oxidative phosphorylation.

<p>Klotho-derived peptide 1 (KP1 human) hydrochloride inhibits the interaction between TGF-β and TGF-β receptor 2, suppressing the activation of TGF-β-induced Smad2/3 and mitogen-activated protein kinase (MAPK). Additionally, it exhibits antifibrotic and renal protective effects in mouse models.</p>

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

KRAS G12C inhibitor 69 (Compound K09) is an inhibitor of the mutant RAS protein KRAS G12C with an IC50 of 4.36 nM. In the cell lines NCI-H358 and MIA-PACA-2, it suppresses ERK phosphorylation with IC50 values of 12 nM and 7 nM, respectively. Additionally, KRAS G12C inhibitor 69 hinders the proliferation of NCI-H358 and MIA-PACA-2 cancer cells, with IC50 values of 3.15 nM and 2.33 nM, respectively.

KS-58 is a derivative of KRpep-2d. It acts as an inhibitory peptide for K-Ras(G12D), selectively binding to K-Ras. KS-58 is capable of penetrating cells and interrupts the interaction between intracellular Ras and effector proteins. It inhibits the proliferation of tumor cells and exhibits antitumor activity.

<p>HPK1-IN-4 is an HPK1 (MAPK41) inhibitor with an IC 50 of 0.061 nM. HPK1-IN-4 is often used as a preclinical immunotherapy tool compound.</p>

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

TAK1-IN-3 is a novel ATP-competitive TAK1 inhibitor for the study of cancer.

<p>Enniatin B1, a Fusarium mycotoxin, crosses the blood-brain barrier and modulates ERK, NF-κB, and ACAT with an IC50 of 73 μM.</p>

LC-2 (PROTAC KRASG12C Degrader-LC-2) is a novel von Hippel-Lindau-based PROTAC degrader of endogenous KRAS G12C with a DC50 between 0.25 and 0.76 μM.LC-2 is a

Anti-ERK2 Antibody (5V598) is a Rabbit antibody targeting ERK2. Anti-ERK2 Antibody (5V598) can be used in ELISA.

Anti-ERK2 Antibody (4F551) is a Rabbit antibody targeting ERK2. Anti-ERK2 Antibody (4F551) can be used in ELISA,FCM.

Anti-ERK2 Antibody (9C922) is a Mouse antibody targeting ERK2. Anti-ERK2 Antibody (9C922) can be used in WB,ELISA.

Enniatins B decreases the activation of ERK (p44/p42).

Tunlametinib is a MEK1/2 inhibitor (IC50=1.9 nM) for treating RAS/RAF-driven cancers.

S6K1-IN-DG2(S6K1InhibitorDG2) is a potent p70S6K inhibitor with an IC50 value of less than 100 nM.

TRPM4 inhibitor 8 is an inhibitor of Transient receptor potential melastatin 4(TRPM4) which contributes to viability, migration, cell cycle shift, and adhesion.

RAS GTPase inhibitor 1 is a RAS GTPase inhibitor with potential antitumor activity.

Cephradine (Standard) is the standard substance of Cephradine, and it is applicable for quantitative analysis, quality control, and related research in biochemical experiments. Cephradine (Anspor) is a beta-lactam, first-generation cephalosporin antibiotic with bactericidal activity.

JH295: potent, selective Nek2 inhibitor (IC50 = 770 nM), irreversibly targets Cys22, no effect on Cdk1, Aurora B, Plk1, or spindle mechanisms.

MLK-IN-1 is a potent and selective mixed-lineage kinase 3 (MLK-3) inhibitor, showing excellent brain penetration and high specificity for MLK-3. MLK-IN-1 at 100 nM supports sustained axonogenesis in cultures challenged with HIV-1 Tat-activated microglia and protects neuronal cells from Tat-induced damage, establishing it as a valuable probe for neuroinflammation and neurodegeneration research.

Nardosinone inhibits H9c2 cell hypertrophy, protects neurons from OGD, and boosts neurite outgrowth by modifying key signaling pathways.

Cefotetan, a cephamycin antibiotic, fights various bacteria by disrupting cell wall synthesis.

BI-882370 is a specific RAF kinase inhibitor.

<p>SGX-523 is a selective Met inhibitor (IC50: 4 nM), no inhibitory to Abl, BRAFV599E, p38α, and c-Raf.</p>

Pyridoxal 5'-phosphate hydrate (PLP)(1:x), the active form of vitamin B6, is a cofactor for many different enzymes involved in transamination reactions,

CID-1067700 is one of the first identified competitive inhibitors of nucleotide binding by Ras-related GTPases（Rab7 with a Ki of 13 nM).

GSK-114, a TNNI3K inhibitor with a 25 nM IC50, is 40x more selective than B-Raf and good for in vivo studies.

<p>PF-06260933 is a highly selective small-molecule MAP4K4 inhibitor with IC50s of 3.7 and 160 nM for kinase and cell, respectively.</p>

Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release.

<p>UM-164 (DAS-DFGO-II), a highly potent c-Src inhibitor with a dissociation constant (Kd) of 2.7 nM, also effectively inhibits p38α and p38β.</p>

NG25 trihydrochloride: kinase inhibitor for MAP4K2, TAK1, Src, LYN, Abl, CSK, FER, p38α; blocks TNF-α signals; impedes IFN secretion; anti-cancer properties.

CC-90001 is an orally administered c-Jun N-terminal kinase (JNK) inhibitor with bias for JNK1 over JNK2.

Kobe 2602 is an inhibitor of Ras that exhibits anticancer chemotherapeutic activities.

NG25 is a potent dual TAK1 and MAP4K2 inhibitor, with IC50s of 149 nM and 21.7 nM, respectively.

IACS-13909 (BBP-398), a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway.

Belvarafenib (HM95573) is a potent pan-RAF inhibitor with antitumor activity and inhibits B-RAF, B-RAFv600E, and C-RAF.Cost-effective and quality-assured.

AZD8330 (ARRY-704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM. Phase 1.

methyl 5-(3,4-dimethoxyphenyl)isoxazole-3-carboxylate is a biochemical.

APS-2-79: KSR-dependent MEK inhibitor, blocks ATP biotin at KSR2, IC50 of 120 nM, disrupts Ras-MAPK signaling.

Refametinib (RDEA119) (RDEA119, Bay 86-9766) is an effective, ATP non-competitive and specific inhibitor of MEK1/2 (IC50: 19/47 nM).

K-Ras(G12C) inhibitor 9 is an allosteric inhibitor of oncogenic K-Ras(G12C).

Cichoric Acid (Dicaffeoyltartaric acid) is a potent inhibitor of human immunodeficiency virus type-1 (HIV-1) integrase and the replication in tissues.

<p>Irreversible K-Ras(G12C) inhibitor 6 fully modifies the protein at 10 μM after 24h in vitro.</p>

GS87 is a highly specific inhibitor of GSK3 (glycogen synthase kinase 3) that induces extensive differentiation of AML cells.