ras-in-2

RMC-6236 is an orally effective and novel triple complex RAS (ON) MULTI inhibitor, which is a potent non covalent inhibitor of multiple RAS variants in GTP binding state. RMC-6236 has anti-tumor activity and can be used in research related to RAS driven tumors. With rich experience in compound synthesis, we can provide fast customized synthesis services for this product according to your research needs.

Pan-RAS-IN-2 (compound 6A) is a molecular glue that specifically targets RAS molecules, exhibiting significant inhibitory activity on the proliferation of RAS-mutated cell lines. It forms a ternary complex with cyclophilin A (CYPA) and RAS(ON) proteins, which blocks the downstream binding of RAF to RAS, thereby exerting antitumor effects.

K-Ras G12C-IN-2 is a covalent KRAS G12C inhibitor.

Pan-KRAS-IN-2 (compound 6) is a broad-spectrum KRAS inhibitor exhibiting potent activity with IC50 values of ≤10 nM against KRAS wild type and its mutants (G12D, G12C, G12V, G12S, G12A, Q61H), while showing significantly reduced inhibition, with an IC50 ＞10 μM, for the KRAS G13D mutant [1].

UCM-1336 (3,3′-(Octylimino)bis[N-phenylpropanamide]) is a potent ICMT inhibitor with an IC50 of 2 μM which is selective against the other enzymes involved in the post-translational modifications of Ras.

1. Oroxylin A (Baicalein 6-methyl ether) has various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion. 2. Oroxylin A possesses abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP LIP CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. 3. Oroxylin A inhibits UCP2s triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells; uncoupling protein 2 plays a key role in mitochondrial apoptotic pathway. 4. Oroxylin A inhibits N1ICD translocating to the nucleus and binding to epithelial-mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. 5. Oroxylin A improves the sensitivity of K562 ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K Akt NF-κB pathway, and probably served as a most promising agent for CML treatment.

K-Ras-IN-1, a K-Ras inhibitor, is characterized by its chemical formula C20H19ClN4O2S and is also known as N-[(1S)-3-cyclopropyl-1-[(6-fluoro-1H-benzimidazol-2-yl)sulfanyl]-2-oxo-1-(phenylmethyl)propyl]-4-fluorobenzenesulfonamide (compound [18, dashboard 819041] in brackets).

K-Ras ligand-Linker Conjugate 2 is a chemical compound that includes a ligand for K-Ras and a PROTAC linker, capable of recruiting E3 ligases like VHL, CRBN, MDM2, and IAP. It is utilized in synthesizing PROTAC K-Ras Degrader-1, a highly effective PROTAC K-Ras degrader with a degradation efficacy of ≥70% in SW1573 cells[1].

YD-3 is a PAR4 antagonist that significantly inhibits thrombin-induced platelet aggregation in rabbits (IC(50)=28.3 microM). In addition, YD-3 suppresses thrombin-induced proliferation of vascular smooth muscle cells (VSMCs) and reduces neointimal thickening after balloon injury. Through Ras- and ERK1 2-mediated signaling pathways, YD-3 impedes thrombin-driven VSMC proliferation. When analyzed with Western blot, YD-3 primarily inhibits thrombin-induced expression of vascular endothelial growth factor receptor 2 (Flk-1) without affecting extracellular signal-regulated kinase 1 2 phosphorylation. YD-3 could potentially have value in elucidating the pathophysiology of thrombin-induced angiogenesis.

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.

PROTAC K-Ras degrader-2 (compound 48) is a broad-spectrum KRAS mutant PROTAC degrader that demonstrates an IC50 of ≤200 nM for KRAS G12V RAF1. Additionally, PROTAC K-Ras degrader-2 achieves a DC50 of ≤200 nM in degrading SW620 KRAS G12D and inhibits the growth of SW620 3D cells with an IC50 of ≤20 nM.

Palmostatin B is a modulator of Ras-signaling that acts by targeting acyl protein thioesterase 1 (APT1) and 2 (APT2) in cells.

CHS-111 is a benzyl indazole compound that inhibits superoxide anion (O(2)(-)) generation and reduces fMLP-stimulated PLD activity (IC(50) 3.9±1.2μM). It inhibits the interaction of PLD1 with ADP-ribosylation factor (Arf) 6 and Ras homology (Rho) A, and reduces the membrane recruitment of RhoA in fMLP-stimulated cells.

CMC2.24 (TRB-N0224) is an orally active tricarbonylmethane agent that demonstrates effectiveness in inhibiting Ras activation and the downstream effector ERK1 2 pathway, thus effectively combating pancreatic tumor formation in mice. Additionally, CMC2.24 exerts potent inhibitory effects on zinc-dependent MMPs, with IC50s ranging from 2.0-69 μM. Furthermore, CMC2.24 aids in alleviating the progression of osteoarthritis by restoring cartilage homeostasis and inhibiting chondrocyte apoptosis through the NF-κB HIF-2α axis[1][2][3].

Alamandine can be formed from angiotensin A by action of ACE-2 or directly from angiotensin-(1-7) by decarboxylation of its aspartate residue. The angiotensin A analog produces effects resembling those of Ang II (1-7). However, it acts independently of the two known vasodilators receptors of the RAS (Mas and angiotensin II type 2). To produce its effects, alamandine binds to the Mas-related receptor, MrgD. A novel orally active formulation of alamandine produced a long-term antihypertensive effect in spontaneously hypertensive rats and cardioprotective effects. These novel findings will be helpful for developing a new understanding of the RAS, a key regulator of blood pressure and fluid balance. The heptapeptide could serve as a model peptide, e.g. in the development and evaluation of analytical methods.

Magnolin reduces the renal oxidative stress, suppresses caspase-3 activity, and increases Bcl-2 expression in vivo and in vitro. Magnolin has anti-inflammatory and antioxidative effects.

ERK-IN-3 benzenesulfonate is a potent and orally active inhibitor of ERK . ERK-IN-3 benzenesulfonate inhibits ERK1 2 with low single-digit nM IC 50 values. ERK-IN-3 benzenesulfonate can be used for the research of cancers driven by RAS mutations.

Pyridostatin Trifluoroacetate Salt is a G-quadruplexe stabilizer with Kd of 490 nM in a cell-free assay, which targets a series of proto-oncogenes including c-kit, K-ras and Bcl-2.

GGTI-286 is a potent, cell permeable GGTase I inhibitor (IC50: 2 μM). GGTI-286 inhibits Rap1A geranylation in NIH3T3 cells (IC50: 2 μM) more potently than H-Ras farnesylation (IC50>30 μM). Ras4B stimulation (IC50: 1 μM).

GGTI-286 hydrochloride is a potent inhibitor of GGTase I (IC50: 2 μM) and is also effective in inhibiting K-Ras4B (IC50: 1 μM). farnesylation (IC50=2 and >30 μM).

MT477 is PKC-α inhibitor. MT477 interfered with PKC activity as well as phosphorylation of Ras and ERK1 2 in H226 human lung carcinoma cells. It also induced poly-caspase-dependent apoptosis. MT477 had a dose-dependent (0.006 to 0.2 mM) inhibitory effect on cellular proliferation of H226, MCF-7, U87, LNCaP, A431 and A549 cancer cell lines as determined by in vitro proliferation assays.

PLX7904 (PB04), also known as PB04, is a potent and selective paradox-breaker RAF inhibitor. It is able to efficiently inhibit activation of ERK1 2 in mutant BRAF melanoma cells but does not hyperactivate ERK1 2 in mutant RAS-expressing cells.

Pimasertib HCl is an orally bioavailable small-molecule inhibitor of MEK1 and MEK2 (MEK1 2) with potential antineoplastic activity. Pimasertib selectively binds to and inhibits the activity of MEK1 2, preventing the activation of MEK1 2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK1 2 (MAP2K1 K2) are dual-specificity threonine tyrosine kinases that play key roles in the activation of the RAS RAF MEK ERK pathway and are often upregulated in a variety of tumor cell types.

GGTI-286 TFA is a potent, cell-permeable inhibitor of GGTase I, exhibiting 25 times greater effectiveness (IC 50 = 2 μM) compared to the corresponding methyl ester of FTI-276. It specifically targets the geranylgeranylation of Rap1A, demonstrating significant selectivity over the farnesylation of H-Ras in NIH3T3 cells (IC 50s = 2 and >30 μM, respectively). Additionally, GGTI-286 TFA effectively inhibits the stimulation of oncogenic K-Ras4B with an IC 50 of 1 μM.