Ras Inhibitor

JMS-053 is an efficient and reversible PTP4A3 inhibitor, with an IC₅₀ value of 18 nM. JMS-053 demonstrates broad PTP4A inhibitory activity with IC₅₀s of 50 nM and 53 nM for PTP4A1 and PTP4A2, respectively. JMS-053 exhibits IC₅₀ values of 92.6 nM and 207.6 nM for CDC25B and DUSP3, respectively. JMS-053 can effectively inhibit the activity of PTP4A3, inhibit tumor cell proliferation and migration through multiple mechanisms such as interfering with RhoA and STAT3/p38 signaling pathway. JMS-053 can be used for the study of cancers such as ovarian cancer, breast cancer and colon cancer.

AZD0022 is a selective and orally active KRAS^G12D inhibitor. AZD0022 inhibits KRAS pathway suppression in the GP2D xenograft model.

RAS inhibitor Abd-7, a potent RAS-binding compound (K_d=51 nM), is a RAS-effector protein-protein interaction (PPI) inhibitor. RAS inhibitor Abd-7 interacts with RAS inside the cells, prevents RAS-effector interactions and inhibits endogenous RAS-dependent signaling. RAS inhibitor Abd-7 impairs the PPI of various mutant KRAS proteins with PI3K, CRAF and RALGDS as well as NRAS Q61H and HRAS G12V.

AM-2383 is a pan KRas inhibitor, can be used for agent resistance in cancer developed with KRas G12C inhibitors.

CCG-100602 is a specific inhibitor of myocardin-related transcription factor A/serum response factor (MRTF-A/SRF) signaling. CCG-100602 specifically block MRTF-A nuclear localization and thus inhibit the fibrogenic transcription factor SRF.

BQU57 is a selective inhibitor of RalA/RalB small GTPases, with a binding potency (Kb) of 7.7 μM for RalB-GDP. BQU57 can block its interaction with effector proteins (such as SEC5 and EXO84), inhibiting tumor cell migration, invasion and non-adherent growth. BQU57 downregulates the NF-κB signaling pathway, reduces the expression of IL-6, IL-8 and MMP-13, and inhibits apoptosis by regulating the Bcl-2/Bax balance. BQU57 also protects the extracellular matrix by inhibiting the Ral/NF-κB pathway and can be used for the study of degenerative diseases. BQU57 exhibits significant antitumor activity in triple-negative breast cancer (TNBC) models, inhibiting orthotopic tumor growth and lung metastasis and enhancing paclitaxel chemotherapy sensitivity.

Elisrasib (D3S-001) is an orally active and selective inhibitor for KRAS. Elisrasib inhibits the proliferation of KRAS^G12C mutant H358 and MIA-PA-CA-2. D3S-001 also inhibits the phosphorylation of cellular ERK1/2. Elisrasib exhibits good metabolic stability in hepatocytes, liver microsomes, plasma and whole blood in various species. D3S-001 exhibits good pharmacokinetic characteristics and antitumor efficacy in mice.

XRP44X inhibits Ras-induced transcription activation with the IC₅₀ of 10 nM. XRP44X inhibits activation of the Ras-Erk-1/2 pathway by FGF-2. XRP44X is an inhibitor of Ras/Erk activation of Elk3 that also affects microtubules.

Digeranyl bisphosphonate (DGBP) is a potent geranylgeranylpyrophosphate (GGPP) synthase inhibitor, which inhibits geranylgeranylation of Rac1.

SHOC2-RAS PPI-IN-1 is a SHOC2-NRAS interaction inhibitor with IC₅₀ of 0.048 μM and a K_d of 0.065 μM for SHOC2. SHOC2-RAS PPI-IN-1 inhibits RAS/MAPK signalling and downregulates MEK and ERK phosphorylation. SHOC2-RAS PPI-IN-1 can inhibit cells proliferation in RAS-mutant cancer models. SHOC2-RAS PPI-IN-1 can be used for the research of RAS-mutant cancers.

Opnurasib (JDQ-443) (NVP-JDQ443) is an orally active, potent, selective, and covalent KRAS G12C inhibitor. Opnurasib shows antitumor activity.

MLS-573151 (MLS000573151) is a selective GTPase Cdc42 inhibitor with an EC₅₀ of 2 μM. MLS-573151 is inactive against other GTPases family members, such as Rab2, Rab7, H-Ras, Rac1, Rac 2 and RhoA wild-type. MLS-573151 acts by blocking the binding of GTP to Cdc42.

ML-097 (CID-2160985) is a pan Ras-related GTPases activator that can activate Rac1, cell division cycle 42, Ras, and Rab7.

Atranorin is a secondary metabolite of lichens and AKT inhibitor. Atranorin possesses multiple activities such as antibacterial, anti-inflammatory, antioxidant, anti-glycation, analgesic, and anti-tumor effects. Atranorin has IC₅₀ values for scavenging DPPH and ABTS free radicals of 117 μM and less than 10 μM, respectively. Additionally, Atranorin also exhibits effects in promoting wound healing. Atranorin can be used in the research of various diseases, including myelodysplastic syndromes, tumors, and inflammatory conditions.

AZA1 is a potent dual inhibitor of Rac1 and Cdc42. AZA1 induces prostate cancer cells apoptosis and inhibits prostate cancer cells proliferation, migration and invasion.

PRLX-93936 dihydrochloride is a molecular Glues that binds to and reprograms the TRIM21 ubiquitin ligase to degrade nuclear pore complexes. PRLX-93936 dihydrochloride binds to TRIM21, forms a ternary complex with TRIM21 and NUP98, and mediates the ubiquitination and proteasomal degradation of NUP98 and other nuclear pore complex proteins. PRLX-93936 dihydrochloride induces the loss of short-lived cytoplasmic mRNA transcripts, triggers cancer cell apoptosis (Apoptosis), and inhibits the activated Ras pathway. PRLX-93936 dihydrochloride inhibits HIF-1 under hypoxic conditions (IC₅₀ = 0.09 μM in cell-based reporter gene assay). PRLX-93936 dihydrochloride suppresses tumor growth in mouse models and improves survival rates in mouse models of multiple myeloma. PRLX-93936 dihydrochloride is applicable to research related to pancreatic cancer and multiple myeloma.

MRTX-1257 is a selective, irreversible, covalent and orally active KRAS G12C inhibitor, with an IC₅₀ of 900 pM for KRAS dependent ERK phosphorylation in H358 cells.

Fendiline, a diphenylalkylamine type of antianginal agent, is an L-type calcium channel blocker (IC₅₀ of 17 µM). Fendiline is also a selective K-Ras inhibitor, and has no effect on H-Ras and N-Ras. Fendiline inhibits K-Ras plasma membrane localization (IC₅₀ of 9.64 μM), inhibits K-Ras signal output and blocks the proliferation of pancreatic, colon, lung, and endometrial cancer cell lines expressing oncogenic mutant K-Ras. Fendiline is a STING agonist and is able to inhibit the growth of multiple refractory cold tumors (MC38, CT26 and B16F10).

AM-001 is a selective Epac1 inhibitor with an IC₅₀ value of 47.8-53.7 μM. AM-001 blocks cAMP (Cyclic AMP) (HY-B1511)-induced conformational changes of Epac1, inhibits Epac1-dependent activation of Rap1, and does not compete with cAMP for binding to Epac1. AM-001 disrupts the formation of the Epac1-GRK5 complex, blocks nuclear import of GRK5, and inhibits GRK5-mediated nuclear export of HDAC5 and activation of MEF2. AM-001 can be used in research related to heart disease, myocardial ischemia/reperfusion injury, SARS-CoV-2 infection, influenza A virus infection, atrial fibrillation and idiopathic pulmonary fibrosis.

Rasarfin is a dual Ras and ARF6 inhibitor.