MAPK

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

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

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

NG 25 is a type II kinase inhibitor targeting multiple kinases with various IC50 values and reduces colorectal cancer cell viability and tumors.

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

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.

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

<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>

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.

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

<p>MRTX1133: Selective inhibitor of KRAS G12D, effective in all protein states, targeting mutant cells.</p>

Anti-inflammatory Agent 7 suppresses proinflammatory cytokines by hindering the NF-κB/MAPK signaling pathway in both LPS-treated RAW 264.7 cells and mice.

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.

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.

PROTAC SOS1 degrader-1: potent, DC50 98.4 nM, inhibits KRAS mutant cancer cells, low-toxic antitumor.

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

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.

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

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.